MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'Mammalian Genome' source. Thu, 09 Feb 2012 09:43:44 +0100 http://www.medworm.com/index.php?rid=5663336&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F7862967w25086744%2F Abstract  In most mammals the growth hormone (GH) locus comprises a single gene expressed primarily in the anterior pituitary gland. However, in higher primates multiple duplications of the GH gene gave rise to a complex locus containing several genes. In man this locus comprises five genes, including GH-N (expressed in pituitary) and four genes expressed in the placenta, but in other species the number and organization of these genes vary. The situation in chimpanzee has been unclear, with suggestions of up to seven GH-like genes. We have re-examined the GH locus in chimpanzee and have deduced the complete sequence. The locus includes five genes apparently organized in a fashion similar to that in human, with two of these genes encoding GH-like proteins, and three encoding ch... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=5663336 Tue, 31 Jan 2012 07:09:39 +0100 5663336 http://www.medworm.com/index.php?rid=5663337&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fx481440195qn84w6%2F This study reports that the presence of the DBA/2J allele results in amelioration or exacerbation of several HD-like phenotypes characteristic of the R6/2 mouse model and indicates the presence of dominant genetic modifiers of HD symptoms. This study is the first step in identifying genes that confer natural genetic variation and modify the HD symptoms. This identification may lead to novel targets for treatment and help elucidate the molecular mechanisms of HD pathogenesis. Content Type Journal ArticlePages 1-11DOI 10.1007/s00335-012-9391-5Authors Randi-Michelle Cowin, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USANghiem Bui, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USADeanna Graha... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=5663337 Tue, 31 Jan 2012 07:09:38 +0100 5663337 http://www.medworm.com/index.php?rid=5642410&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F5u674121537842rl%2F Abstract  We review the underlying principles and tools used in genomic studies of domestic dogs aimed at understanding the genetic changes that have occurred during domestication. We show that there are two principle modes of evolution within dogs. One primary mode that accounts for much of the remarkable diversity of dog breeds is the fixation of discrete mutations of large effect in individual lineages that are then crossed to various breed groupings. This transfer of mutations across the dog evolutionary tree leads to the appearance of high phenotypic diversity that in actuality reflects a small number of major genes. A second mechanism causing diversification involves the selective breeding of dogs within distinct phenotypic or functional groups, which enhances specifi... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=5642410 Tue, 24 Jan 2012 06:54:36 +0100 5642410 http://www.medworm.com/index.php?rid=5623724&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fq6j4822q87074347%2F Abstract  Genome-wide mutagenesis was performed in mice to identify candidate genes for male infertility, for which the predominant causes remain idiopathic. Mice were mutagenized using N-ethyl-N-nitrosourea (ENU), bred, and screened for phenotypes associated with the male urogenital system. Fifteen heritable lines were isolated and chromosomal loci were assigned using low-density genome-wide SNP arrays. Ten of the 15 lines were pursued further using higher-resolution SNP analysis to narrow the candidate gene regions. Exon sequencing of candidate genes identified mutations in mice with cystic kidneys (Bicc1), cryptorchidism (Rxfp2), restricted germ cell deficiency (Plk4), and severe germ cell deficiency (Prdm9). In two other lines with severe hypogonadism, candidate sequencin... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=5623724 Thu, 19 Jan 2012 06:55:00 +0100 5623724 http://www.medworm.com/index.php?rid=5623723&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fh5l6k7hu63516834%2F Content Type Journal ArticlePages 1-2DOI 10.1007/s00335-012-9389-zAuthors Elaine A. Ostrander, Cancer Genetics Branch, National Human Genome Research Institute, NIH, 50 South Drive, Building 50, Room 5351, Bethesda, MD 20892, USA Journal Mammalian GenomeOnline ISSN 1432-1777Print ISSN 0938-8990 (Source: Mammalian Genome) Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=5623723 Thu, 19 Jan 2012 06:55:00 +0100 5623723 http://www.medworm.com/index.php?rid=5590876&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ft87gv2388464k302%2F Abstract  A rose may be a rose by any other name, but when you call a dog a poodle it becomes a very different animal than if you call it a bulldog. Both the poodle and the bulldog are examples of dog breeds of which there are >400 recognized worldwide. Breed creation has played a significant role in shaping the modern dog from the length of his leg to the cadence of his bark. The selection and line-breeding required to maintain a breed has also reshaped the genome of the dog, resulting in a unique genetic pattern for each breed. The breed-based population structure combined with extensive morphologic variation and shared human environments have made the dog a popular model for mapping both simple and complex traits and diseases. In order to obtain the most benefit from ... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=5590876 Mon, 09 Jan 2012 19:35:36 +0100 5590876 http://www.medworm.com/index.php?rid=5567089&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F30vr1r463528754r%2F Abstract  Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder in which the loss of dystrophin causes progressive degeneration of skeletal and cardiac muscle. Potential therapies that carry substantial risk, such as gene- and cell-based approaches, must first be tested in animal models, notably the mdx mouse and several dystrophin-deficient breeds of dogs, including golden retriever muscular dystrophy (GRMD). Affected dogs have a more severe phenotype, in keeping with that of DMD, so may better predict disease pathogenesis and treatment efficacy. Various phenotypic tests have been developed to characterize disease progression in the GRMD model. These biomarkers range from measures of strength and joint contractures to magnetic resonance imaging. Some of these... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=5567089 Wed, 04 Jan 2012 17:02:40 +0100 5567089 http://www.medworm.com/index.php?rid=5567090&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fw515820019464373%2F Abstract  Tardive dyskinesia (TD) is a debilitating, unpredictable, and often irreversible side effect resulting from chronic treatment with typical antipsychotic agents such as haloperidol. TD is characterized by repetitive, involuntary, purposeless movements primarily of the orofacial region. In order to investigate genetic susceptibility to TD, we used a validated mouse model for a systems genetics analysis geared toward detecting genetic predictors of TD in human patients. Phenotypic data from 27 inbred strains chronically treated with haloperidol and phenotyped for vacuous chewing movements were subject to a comprehensive genomic analysis involving 426,493 SNPs, 4,047 CNVs, brain gene expression, along with gene network and bioinformatic analysis. Our results identifie... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=5567090 Fri, 30 Dec 2011 07:08:03 +0100 5567090 http://www.medworm.com/index.php?rid=5541597&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fn41573201603100w%2F Abstract  Mice genetically engineered to express human FcRn are valuable models for the evaluation of therapeutic antibodies in the context of human FcRn in vivo. However, only limited clinical chemistry information on these mouse strains is available. Thus, we have compared 30 clinical chemical parameters of C57BL/6J wild-type mice, murine FcRn-knockout mice, and two human FcRn transgenic mouse strains expressing human FcRn in the absence of murine FcRn. Since FcRn-mediated recycling prevents albumin and IgG from intracellular degradation, significant differences for both proteins were observed in the murine FcRn-knockout mice. Mice lacking FcRn show lower IgG and albumin levels compared to wild-type mice. The most prominent differences in clinical chemical parameters can ... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=5541597 Thu, 22 Dec 2011 16:37:13 +0100 5541597 http://www.medworm.com/index.php?rid=5541599&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fm818815277h45160%2F Abstract  Much of the DNA in genomes is organized within gene families and hierarchies of gene superfamilies. DNA methylation is the main epigenetic event involved in gene silencing and genome stability. In the present study, we analyzed the DNA methylation status of the prolactin (PRL) superfamily to obtain insight into its tissue-specific expression and the evolution of its sequence diversity. The PRL superfamily in mice consists of two dozen members, which are expressed in a tissue-specific manner. The genes in this family have CpG-less sequences, and they are located within a 1-Mb region as a gene cluster on chromosome 13. We tentatively grouped the family into several gene clusters, depending on location and gene orientation. We found that all the members had tissue-depe... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=5541599 Thu, 22 Dec 2011 16:37:12 +0100 5541599 http://www.medworm.com/index.php?rid=5541598&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fw731207p57821h74%2F This study establishes a unique model of canine RD requiring homozygous mutations at two distinct genetic loci for the manifestation of early-onset RD. Content Type Journal ArticlePages 1-12DOI 10.1007/s00335-011-9384-9Authors Keiko Miyadera, Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge, CB3 0ES UKKumiko Kato, Department of Veterinary Medical Science, Graduate School of Agricultural and Life Sciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, JapanMike Boursnell, Centre for Preventive Medicine, Animal Health Trust, Lanwades Park, Kentford, Newmarket, Suffolk CB8 7UU, UKCathryn S. Mellersh, Centre for Preventive Medicine, Animal Health Trust, Lanwades Park, Kentford, Newmarket, Suffolk CB8 7UU, UKDavid R. Sargan, Department... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=5541598 Thu, 22 Dec 2011 16:37:12 +0100 5541598 http://www.medworm.com/index.php?rid=5510699&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F51j8182217043832%2F Abstract  Calcium-modulating cyclophilin ligand (Caml) is a ubiquitously expressed cytoplasmic protein that is involved in multiple signaling and developmental pathways. An observation in our laboratory of a protein–protein interaction between Caml and the cytoplasmic region of Cadherin23 led us to speculate that Caml might be important in the inner ear and play a role in the development and/or function of hair cells. To address this question, we generated a mouse line in which Caml expression was eliminated in Atoh1-expressing cells of the inner ear upon administration of tamoxifen. Tamoxifen was administered immediately after birth to neonates to assess the effect of loss of Caml in the inner ear during postnatal development. Hearing in treated animals was tested by audi... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=5510699 Wed, 14 Dec 2011 16:43:18 +0100 5510699 http://www.medworm.com/index.php?rid=5491457&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F875300m3m2700651%2F Abstract  Tumor location can profoundly affect morbidity and patient prognosis, even for the same tumor type. Very little is known about whether tumor location is determined stochastically or whether genetic risk factors can affect where tumors arise within an organ system. We have taken advantage of the Nf1−/+;Trp53−/+cis mouse model of astrocytoma/glioblastoma to map genetic loci affecting whether astrocytomas are found in the spinal cord. We identify a locus on distal Chr 5, termed Scram1 for spinal cord resistance to astrocytoma modifier 1, with a LOD score of 5.0 and a genome-wide significance of P < 0.004. Mice heterozygous for C57BL/6J×129S4/SvJae at this locus show less astrocytoma in the spinal cord compared to 129S4/SvJae homozygous mice, although ... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=5491457 Wed, 07 Dec 2011 16:44:24 +0100 5491457 http://www.medworm.com/index.php?rid=5491458&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fa68412387321qj2k%2F This article reviews the work that has been done on the Bedlington terrier, summarizes what was learned from studies into COMMD1 function, describes hereditary copper toxicosis phenotypes in other dog breeds, and discusses the opportunities for genome-wide association studies on copper toxicosis in the dog to contribute to the understanding of mammalian copper metabolism and copper metabolism disorders in man. Content Type Journal ArticlePages 1-14DOI 10.1007/s00335-011-9378-7Authors Hille Fieten, Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 108, 3584 CM Utrecht, The NetherlandsPeter A. J. Leegwater, Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Yalela... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=5491458 Tue, 06 Dec 2011 17:04:51 +0100 5491458 http://www.medworm.com/index.php?rid=5481656&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fl7077063x1811p32%2F Abstract  Differences in the content and organization of DNA, collectively referred to as structural variation, have emerged as a major source of genetic and phenotypic diversity within and between species. In addition, structural variation provides an important substrate for evolutionary innovations. Here, we review recent progress in characterizing patterns of canine structural variation within and between breeds, and in correlating copy number variants (CNVs) with phenotypes. Because of the extensive phenotypic diversity that exists within and between breeds and the tantalizing examples of canine CNVs that influence traits such as skin wrinkling in Shar-Pei, dorsal hair ridge in Rhodesian and Thai Ridgebacks, and short limbs in many breeds such as Dachshunds and Corgis, ... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=5481656 Sat, 03 Dec 2011 16:48:45 +0100 5481656 http://www.medworm.com/index.php?rid=5481657&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fm3408j646171758h%2F Abstract  The human complex diseases such as hypertension, precocious puberty, and diabetes have their own diagnostic thresholds, which are usually estimated from the epidemiological data of nature populations. In the mouse models, numerous phenotypic data of complex traits have been accumulated; however, knowledge of the phenotypic distribution of the natural mouse populations remains quite limited. In order to investigate the distribution of quantitative traits of wild mice, 170 F1 progeny aged 8–10 weeks and derived from wild mice collected from eight spots in the suburbs of Shanghai were tested for their values of anatomic, blood chemical, and blood hematological parameters. All the wild mice breeders were of Mus. m. musculus and Mus. m. castaneus maternal origin ... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=5481657 Fri, 02 Dec 2011 18:09:25 +0100 5481657 http://www.medworm.com/index.php?rid=5453116&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fl06pr421x645223n%2F Abstract  The silver fox provides a rich resource for investigating the genetics of behavior, with strains developed by intensely selective breeding that display markedly different behavioral phenotypes. Until recently, however, the tools for conducting molecular genetic investigations in this species were very limited. In this review, the history of development of this resource and the tools to exploit it are described. Although the focus is on the genetics of domestication in the silver fox, there is a broader context. In particular, one expectation of the silver fox research is that it will be synergistic with studies in other species, including humans, to yield a more comprehensive understanding of the molecular mechanisms and evolution of a wider range of social cognit... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=5453116 Tue, 22 Nov 2011 18:00:05 +0100 5453116 http://www.medworm.com/index.php?rid=5453117&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F5h987mu0n48083j2%2F Abstract  The German Shepherd Dog (GSD) is a popular working and companion breed for which over 50 hereditary diseases have been documented. Herein, SNP profiles for 197 GSDs were generated using the Affymetrix v2 canine SNP array for a genome-wide association study to identify loci associated with four diseases: pituitary dwarfism, degenerative myelopathy (DM), congenital megaesophagus (ME), and pancreatic acinar atrophy (PAA). A locus on Chr 9 is strongly associated with pituitary dwarfism and is proximal to a plausible candidate gene, LHX3. Results for DM confirm a major locus encompassing SOD1, in which an associated point mutation was previously identified, but do not suggest modifier loci. Several SNPs on Chr 12 are associated with ME and a 4.7 Mb haplotype block is pr... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=5453117 Tue, 22 Nov 2011 06:57:00 +0100 5453117 http://www.medworm.com/index.php?rid=5446410&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F7l88vt26051rw103%2F Abstract  Alaskan sled dogs are a genetically distinct population shaped by generations of selective interbreeding with purebred dogs to create a group of high-performance athletes. As a result of selective breeding strategies, sled dogs present a unique opportunity to employ admixture-mapping techniques to investigate how breed composition and trait selection impact genomic structure. We used admixture mapping to investigate genetic ancestry across the genomes of two classes of sled dogs, sprint and long-distance racers, and combined that with genome-wide association studies (GWAS) to identify regions that correlate with performance-enhancing traits. The sled dog genome is enhanced by differential contributions from four non-admixed breeds (Alaskan Malamute, Siberian Husky... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=5446410 Mon, 21 Nov 2011 18:09:20 +0100 5446410 http://www.medworm.com/index.php?rid=5446411&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fb146531k81110547%2F Abstract  BLAST analysis of the rat genome revealed the presence of 16 pseudogenes of isoform 1 of the mitochondrial voltage-dependent anion channel (VDAC1). Based on their structural characterization, it was concluded that these pseudogenes were formed by integration of VDAC1 cDNA into the genome, and subsequent rearrangements/mutations. By RT-PCR analysis using carefully designed primers that could not amplify the cDNA of genuine VDAC1, 8 of these 16 pseudogenes showed slight expression in certain tissues, but none of them seemed to encode a functional protein. Content Type Journal ArticlePages 1-8DOI 10.1007/s00335-011-9375-xAuthors Yusuke Ido, Institute for Genome Research, University of Tokushima, Kuramoto-cho-3, Tokushima, 770-8503 JapanTakenori Yamamoto, Institu... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=5446411 Sat, 19 Nov 2011 16:54:46 +0100 5446411 http://www.medworm.com/index.php?rid=5446412&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj32675570p427011%2F Abstract  Strain-specific differences in susceptibility to mouse adenovirus type 1 (MAV-1) are linked to the quantitative trait locus Msq1 on mouse chromosome 15. This region contains 14 Ly6 or Ly6-related genes, many of which are known to be expressed on the surface of immune cells, suggesting a possible role in host defense. We analyzed these genes for polymorphisms between MAV-1-susceptible and MAV-1-resistant inbred mouse strains. Sequencing of cDNAs identified 12 coding-region polymorphisms in 2010109I03Rik, Ly6e, Ly6a, Ly6c1, and Ly6c2, six of which were nonsynonymous and five of which were previously unlisted in dbSNP Build 132. We also clarified sequence discrepancies in GenBank for the coding regions of I830127L07Rik and Ly6g. Additionally, Southern blotting revealed... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=5446412 Sat, 19 Nov 2011 16:54:45 +0100 5446412 http://www.medworm.com/index.php?rid=5415585&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F180133572786p767%2F Abstract  Olfaction is a particularly important sense in the dog. Humans selected for this capacity during the domestication process, and selection has continued to be employed to enhance this ability. In this review we first describe the different olfactory systems that exist and the different odorant receptors that are expressed in those systems. We then focus on the dog olfactory receptors by describing the olfactory receptor gene repertoire and its polymorphisms. Finally, we discuss the different uses of dog olfaction and the questions that still need to be studied. Content Type Journal ArticlePages 1-12DOI 10.1007/s00335-011-9371-1Authors Pascale Quignon, Institut de Génétique et Développement de Rennes, UMR6061 CNRS Université de Rennes 1, Faculté de Médeci... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=5415585 Sat, 12 Nov 2011 16:52:46 +0100 5415585 http://www.medworm.com/index.php?rid=5415586&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F031825p473055378%2F Abstract  The mapping of the canine genome and the study of canine breed genomic architecture has revolutionized the discovery of genetic tests for inherited disorders in dogs. As the genetics underlying complex disorders are revealed, canine breeders and their registering organisations will be required to understand genetics in a much more sophisticated way. To facilitate the management of genetic disorders in the era of new complex information, we consider how best to apply the results of new research and analytical techniques to benefit the wider canine breeding community with the aims of improving canine health and maintaining benevolent genetic diversity. If this is not done, there is a serious risk that expensive and valuable genetic research will remain unused or be ... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=5415586 Fri, 11 Nov 2011 16:45:23 +0100 5415586 http://www.medworm.com/index.php?rid=5415587&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F3670470174k5jl14%2F Abstract  There are over 350 genetically distinct breeds of domestic dog that present considerable variation in morphology, physiology, and disease susceptibility. The genome sequence of the domestic dog was assembled and released in 2005, providing an estimated 20,000 protein-coding genes that are a great asset to the scientific community that uses the dog system as a genetic biomedical model and for comparative and evolutionary studies. Although the canine gene set had been predicted using a combination of ab initio methods, homology studies, motif analysis, and similarity-based programs, it still requires a deep annotation of noncoding genes, alternative splicing, pseudogenes, regulatory regions, and gain and loss events. Such analyses could benefit from new sequencing t... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=5415587 Thu, 10 Nov 2011 16:55:16 +0100 5415587 http://www.medworm.com/index.php?rid=5415588&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fjq73400k37285360%2F Abstract  Animal models that closely resemble human disease can present a challenge. Particularly so in alpha-1 antitrypsin deficiency (α1ATD), as the mouse alpha-1 antitrypsin (α1AT) cluster encodes five highly related genes compared with the one in humans. The mouse PI2 homologue is closest to the α1AT human gene. We have changed the equivalent mouse site that results in the Z variant in man (Glu342Lys) and made both the “M” and “Z” mouse PI2 α1AT proteins. We have tested the ability of a small-molecular-weight compound CG to alleviate polymerisation of these mouse α1AT proteins as it has been shown to reduce aggregates of Z α1AT in man. We found that (1) CG specifically reduces the formation of polymers of recombinant mouse “Z” protein but not “M” pro... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=5415588 Thu, 10 Nov 2011 16:55:15 +0100 5415588 http://www.medworm.com/index.php?rid=5415589&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fg0434425nv0314g0%2F Abstract  There are currently about 80 different DNA tests available for mutations that are associated with inherited disease in the domestic dog, and as the tools available with which to dissect the canine genome become increasingly sophisticated, this number can be expected to rise dramatically over the next few years. With unrelenting media pressure focused firmly on the health of the purebred domestic dog, veterinarians and dog breeders are turning increasingly to DNA tests to ensure the health of their dogs. It is ultimately the responsibility of the scientists who identify disease-associated genetic variants to make sensible choices about which discoveries are appropriate to develop into commercially available DNA tests for the lay dog breeder, who needs to balance th... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=5415589 Wed, 09 Nov 2011 17:58:54 +0100 5415589 http://www.medworm.com/index.php?rid=5415590&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fn653g65rt1224p62%2F Abstract  Considerable clinical and molecular variations have been known in retinal blinding diseases in man and also in dogs. Different forms of retinal diseases occur in specific breed(s) caused by mutations segregating within each isolated breeding population. While molecular studies to find genes and mutations underlying retinal diseases in dogs have benefited largely from the phenotypic and genetic uniformity within a breed, within- and across-breed variations have often played a key role in elucidating the molecular basis. The increasing knowledge of phenotypic, allelic, and genetic heterogeneities in canine retinal degeneration has shown that the overall picture is rather more complicated than initially thought. Over the past 20 years, various approaches have be... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=5415590 Tue, 08 Nov 2011 06:47:19 +0100 5415590 http://www.medworm.com/index.php?rid=5394477&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fyh45045r673r7561%2F Abstract  Congenital disorders of the hepatic portal vasculature are rare in man but occur frequently in certain dog breeds. In dogs, there are two main subtypes: intrahepatic portosystemic shunts, which are considered to stem from defective closure of the embryonic ductus venosus, and extrahepatic shunts, which connect the splanchnic vascular system with the vena cava or vena azygos. Both subtypes result in nearly complete bypass of the liver by the portal blood flow. In both subtypes the development of the smaller branches of the portal vein tree in the liver is impaired and terminal branches delivering portal blood to the liver lobules are often lacking. The clinical signs are due to poor liver growth, development, and function. Patency of the ductus venosus seems to be ... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=5394477 Thu, 03 Nov 2011 16:54:19 +0100 5394477 http://www.medworm.com/index.php?rid=5394476&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F07341964128pp8u2%2F Abstract  Osteochondrosis is a developmental orthopaedic disease that occurs in horses, other livestock species, companion animal species, and humans. The principal aim of this study was to identify quantitative trait loci (QTL) associated with osteochondritis dissecans (OCD) in the Thoroughbred using a genome-wide association study. A secondary objective was to test the effect of previously identified QTL in the current population. Over 300 horses, classified as cases or controls according to clinical findings, were genotyped for the Illumina Equine SNP50 BeadChip. An animal model was first implemented in order to adjust each horse’s phenotypic status for average relatedness among horses and other potentially confounding factors which were present in the data. The genome... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=5394476 Thu, 03 Nov 2011 16:54:19 +0100 5394476 http://www.medworm.com/index.php?rid=5372176&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fp21143q9kl35g916%2F Content Type Journal ArticleCategory ErratumPages 1-1DOI 10.1007/s00335-011-9367-xAuthors Laura G. Reinholdt, The Jackson Laboratory, Genetic Resource Science, 600 Main St., Bar Harbor, ME 04609, USAYueming Ding, Regeneron Pharmaceuticals Inc., 777 Old Saw Mill River Road, Tarrytown, NY 10591, USAGriffith J. Gilbert, The Jackson Laboratory, Genetic Resource Science, 600 Main St., Bar Harbor, ME 04609, USAAnne Czechanski, The Jackson Laboratory, Genetic Resource Science, 600 Main St., Bar Harbor, ME 04609, USAJeffrey P. Solzak, Department of Biology, Indiana University-Purdue University Indianapolis, 723 W. Michigan Street, SL 306, Indianapolis, IN 46202, USARandall J. Roper, Department of Biology, Indiana University-Purdue University Indianapolis, 723 W. Michigan Street, SL 306, Indi... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=5372176 Mon, 31 Oct 2011 16:53:48 +0100 5372176 http://www.medworm.com/index.php?rid=5372177&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fe24q3q1569057386%2F Abstract  There has been much interest in utilizing the dog as a genetic model for common human diseases. Both dogs and humans suffer from naturally occurring epilepsies that share many clinical characteristics. Investigations of inherited human epilepsies have led to the discovery of several mutated genes involved in this disease; however, the vast majority of human epilepsies remain unexplained. Mouse models of epilepsy exist, including single-gene spontaneous and knockout models, but, similar to humans, other, polygenic models have been more difficult to discern. This appears to also be the case in canine epilepsy genetics. There are two forms of canine epilepsies for which gene mutations have been described to date: the progressive myoclonic epilepsies (PMEs) and idiopa... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=5372177 Sun, 30 Oct 2011 05:37:59 +0100 5372177 http://www.medworm.com/index.php?rid=5372178&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fv57u153188226761%2F Abstract  Adrenocortical dysplasia (acd) is a spontaneous autosomal recessive mouse mutation exhibiting caudal truncation, vertebral segmentation defects, hydronephrosis, limb hypoplasia, and perinatal lethality. Acd encodes TPP1, a component of the shelterin complex that maintains telomere integrity, and consequently acd mutant mice have telomere dysfunction and genomic instability. We previously showed that apoptosis is the primary mechanism causing the acd skeletal phenotype, and that p53 deficiency rescues the skeletal defects of the acd phenotype but has no effect on the perinatal lethality. The Trp63 gene encodes multiple isoforms, which play a role in proliferation, apoptosis, and stem/progenitor cell maintenance. Different p63 isoforms exhibit both proapoptotic (TAp63)... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=5372178 Fri, 28 Oct 2011 17:16:26 +0100 5372178 http://www.medworm.com/index.php?rid=5329093&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fn2l6j6j7lv211676%2F Abstract  The Rinshoken cataract (rct) mutation, which causes congenital cataracts, is a recessive mutation found in SJL/J mice. All mutants present with opacity in the lens by 2 months of age. The rct locus was mapped to a 1.6-Mb region in Chr 4 that contains the Foxe3 gene. This gene is responsible for cataracts in humans and mice, and it plays a crucial role in the development of the lens. Furthermore, mutation of Foxe3 causes various ocular defects. We sequenced the genomic region of Foxe3, including the coding exons and UTRs; however, no mutations were discovered in these regions. Because there were no differences in Foxe3 sequences between the rct/rct and wild-type mice, we inferred that a mutation was located in the regulatory regions of the Foxe3 gene. To test thi... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=5329093 Fri, 14 Oct 2011 10:46:21 +0100 5329093 http://www.medworm.com/index.php?rid=5329094&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F22rur51x3082w145%2F Abstract  The mutation of the Wilson’s disease protein ATP7B has been widely used to study the direct link between hepatic high copper and development of liver pathology. Several studies have used gene expression profiling of high-copper effects to identify the key genes in the process, but few focused on the involved pathways and the coexpression patterns of associated pathways. We used a microarray data set from the public database library of GEO (Gene Expression Omnibus), which is associated with liver transcriptome in the early stages of copper accumulation in the mouse model of Wilson’s disease under Atp7b knockout. To be more powerful than conventional single-gene methods in the study of complex diseases, we applied gene set enrichment analysis (GSEA) on the data s... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=5329094 Fri, 14 Oct 2011 05:50:42 +0100 5329094 http://www.medworm.com/index.php?rid=5280058&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj47660484764h782%2F Abstract  Ts65Dn is a mouse model of Down syndrome: a syndrome that results from chromosome (Chr) 21 trisomy and is associated with congenital defects, cognitive impairment, and ultimately Alzheimer’s disease. Ts65Dn mice have segmental trisomy for distal mouse Chr 16, a region sharing conserved synteny with human Chr 21. As a result, this strain harbors three copies of over half of the human Chr 21 orthologs. The trisomic segment of Chr 16 is present as a translocation chromosome (Mmu1716), with breakpoints that have not been defined previously. To molecularly characterize the Chrs 16 and 17 breakpoints on the translocation chromosome in Ts65Dn mice, we used a selective enrichment and high-throughput paired-end sequencing approach. Analysis of paired-end reads flanking th... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=5280058 Wed, 28 Sep 2011 05:49:45 +0100 5280058 http://www.medworm.com/index.php?rid=5280059&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fr76722672n151682%2F Abstract  Down syndrome (DS) is the most frequent genetic disorder leading to intellectual disabilities and is caused by three copies of human chromosome 21. Mouse models are widely used to better understand the physiopathology in DS or to test new therapeutic approaches. The older and the most widely used mouse models are the trisomic Ts65Dn and the Ts1Cje mice. They display deficits similar to those observed in DS people, such as those in behavior and cognition or in neuronal abnormalities. The Ts65Dn model is currently used for further therapeutic assessment of candidate drugs. In both models, the trisomy was induced by reciprocal chromosomal translocations that were not further characterized. Using a comparative genomic approach, we have been able to locate precisely th... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=5280059 Wed, 28 Sep 2011 05:49:42 +0100 5280059 http://www.medworm.com/index.php?rid=5173420&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F3107v3405177q155%2F In this study, MeDIP and Sequenom MassARRAY were used to identify hypomethylated gene promoters in the human placenta. Among the genes identified, the hypomethylation of an alternative promoter for KCNH5 was found to be restricted to the placenta and chorion. Complete methylation of this promoter correlates with a silenced KCNH5 transcript in embryonic tissues, including the amnion. Unusually, this hypomethylated promoter and the alternative first exon are derived from a SINE (AluY) retrotransposon. Examination of additional retrotransposon-derived gene promoters in the placenta confirmed that retrotransposon hypomethylation permits the placenta-specific expression of these genes. Furthermore, the lineage-specific methylation displayed by KCNH5, INSL4, and ERVWE1 revealed that dichoto... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=5173420 Sat, 27 Aug 2011 05:57:13 +0100 5173420 http://www.medworm.com/index.php?rid=5153412&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F17k51383141h0k46%2F Abstract  Lens opacity 13 (lop13) is a spontaneous, autosomal recessive mouse mutant that exhibits nuclear cataracts. Histological analysis revealed swollen lens fiber cells and the presence of bladder cells within the lens cortex, as well as morgagnian globules and liquefied material at the lens posterior. At 3 months of age, in addition to cataracts, lop13 mice also develop persistent skin wounds. Linkage analysis assigned the lop13 locus to a 1.1-Mb region on mouse Chr 15, encompassing 19 candidate genes. Sequence analysis identified a C3112T mutation in exon 18 of Sterol Regulatory Element Binding-Transcription Factor 2 (Srebf2) resulting in the R1038C substitution of a highly conserved arginine within the Srebf2 regulatory domain. Srebf2 belongs to a family of membr... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=5153412 Sun, 21 Aug 2011 05:36:56 +0100 5153412 http://www.medworm.com/index.php?rid=5153413&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fn45m2316822h3785%2F Abstract  In the present study, dissection of genetic bases of testis weight in mice was performed. Autosomes and the X chromosome were searched using traditional quantitative trait locus (QTL) scans, and the Y chromosome was searched by association studies of Y-consomic strains. QTL analysis was performed in ♀DDD × ♂CBA F2 mice; the inbred mouse DDD has the heaviest testes, whereas the inbred mouse CBA has the lightest testes. Two significant testis weight QTLs were identified on chromosomes 1 and X. A DDD allele was associated with increased and decreased testis weight at the locus on chromosomes 1 and X, respectively. In the reciprocal cross ♀CBA × ♂DDD F2 mice, QTL on chromosome 1, and not on chromosome X, had a significant effect on testis w... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=5153413 Sat, 20 Aug 2011 15:52:34 +0100 5153413 http://www.medworm.com/index.php?rid=5084503&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fu577553170532235%2F In this study, linkage and linkage disequilibrium analysis (LDLA) for four carcass traits was undertaken using 19 markers on bovine chromosome 14. The LDLA analysis detected quantitative trait loci (QTL) for carcass weight (CWT) and eye muscle area (EMA) at the same position at around 50 cM and surrounded by the markers FABP4SNP2774C>G and FABP4_μsat3237. The QTL for marbling (MAR) was identified at the midpoint of markers BMS4513 and RM137 in a 3.5-cM marker interval. The most likely position for a second QTL for CWT was found at the midpoint of tenth marker bracket (FABP4SNP2774C>G and FABP4_μsat3237). For this marker bracket, the total number of haplotypes was 34 with a most common frequency of 0.118. Effects of haplotypes on CWT varied from a −5-kg deviation for hapl... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=5084503 Sat, 30 Jul 2011 05:58:39 +0100 5084503 http://www.medworm.com/index.php?rid=5075057&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fg12n44x368810554%2F Content Type Journal ArticlePages 1-1DOI 10.1007/s00335-011-9352-4Authors Steve D. M. Brown, Medical Research Council, Mammalian Genetics Unit, Harwell, Didcot, Oxfordshire, OX11 ORD UK Journal Mammalian GenomeOnline ISSN 1432-1777Print ISSN 0938-8990 (Source: Mammalian Genome) Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=5075057 Wed, 27 Jul 2011 18:48:12 +0100 5075057 http://www.medworm.com/index.php?rid=5060896&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F21467858187155g8%2F In this study we used a unique approach for targeted, single-copy transgene insertion to generate transgenic mice carrying a Mthfr upstream or Mthfr downstream promoter-reporter construct located 5′ to the endogenous Hprt (hypoxanthine-guanine phosphoribosyltransferase) locus. The Mthfr downstream promoter demonstrated activity in the neural tube, neural crest cells, dorsal root ganglia, heart, and endothelial cells of blood vessels in 10.5-days post coitum embryos and placentas. Upstream promoter activity was absent at this developmental stage. Postnatally, both promoters demonstrated activity in the brain stem, hippocampus, and thalamus of 1-week-old brain that became stronger in the adult. The Mthfr upstream promoter also showed activity in the cerebellum and cerebral cortex. Both... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=5060896 Tue, 19 Jul 2011 06:42:04 +0100 5060896 http://www.medworm.com/index.php?rid=5060895&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fa26542w4r38m0748%2F Abstract  X Chromosome inactivation (XCI) silences one copy of most X-linked genes in female mammals. Notably, human and mouse differ strikingly in the number and organization of the genes that escape XCI. While on the human X Chromosome (Chr) escape genes are organized in domains, the few known genes that escape inactivation in the mouse appear to be isolated. Here we characterize the gene Cxorf26 and adjacent noncoding transcripts that map to XqD. We assess allelic expression in a nonrandomly X-inactivated cell line and directly demonstrate that 2610029G23Rik (Cxorf26) and its head-to-head neighbor (5530601H04Rik) escape X inactivation, creating a small escape domain. Both genes are robustly expressed from the inactive X Chr at approximately 50 and 30% of the expression le... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=5060895 Tue, 19 Jul 2011 06:42:04 +0100 5060895 http://www.medworm.com/index.php?rid=5046564&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F773463j442704135%2F Abstract  The present study measured variation in body weight using a combined analysis in an F2 intercross and an F34 advanced intercross line (AIL). Both crosses were derived from inbred LG/J and SM/J mice, which were selected for large and small body size prior to inbreeding. Body weight was measured at 62 (±5) days of age. Using an integrated GWAS and forward model selection approach, we identified 11 significant QTLs that affected body weight on ten different chromosomes. With these results we developed a full model that explained over 18% of the phenotypic variance. The median 1.5-LOD support interval was 5.55 Mb, which is a significant improvement over most prior body weight QTLs. We identified nonsynonymous coding SNPs between LG/J and SM/J mice in order to further ... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=5046564 Fri, 15 Jul 2011 05:52:30 +0100 5046564 http://www.medworm.com/index.php?rid=5015972&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fc21501440n107p18%2F Abstract  The domestic dog is of great benefit to humankind, not only through companionship and working activities cultivated through domestication and selective breeding, but also as a model for biomedical research. Many single-gene traits have been well-characterized at the genomic level, and recent advances in whole-genome association studies will allow for better understanding of complex, multigenic hereditary diseases. Additionally, the dog serves as an invaluable large animal model for assessment of novel therapeutic agents. Thus, the dog has filled a crucial step in the translation of basic research to new treatment regimens for various human diseases. Four well-characterized diseases in canine models are discussed as they relate to other animal model availability, n... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=5015972 Wed, 06 Jul 2011 06:35:26 +0100 5015972 http://www.medworm.com/index.php?rid=5015974&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F3376155057517760%2F Abstract  Iron homeostasis is crucial to many biological functions in nearly all organisms, with roles ranging from oxygen transport to immune function. Disruption of iron homeostasis may result in iron overload or iron deficiency. Iron deficiency may have severe consequences, including anemia or changes in immune or neurotransmitter systems. Here we report on the variability of phenotypic iron tissue loss and splenomegaly and the associated quantitative trait loci (QTLs), polymorphic areas in the mouse genome that may contain one or more genes that play a role in spleen iron concentration or spleen weight under each dietary treatment. Mice from 26 BXD/Ty recombinant inbred strains, including the parent C57BL/6 and DBA/2 strains, were randomly assigned to adequate iron or i... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=5015974 Wed, 06 Jul 2011 06:35:23 +0100 5015974 http://www.medworm.com/index.php?rid=5015973&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fbgt1687551k41146%2F Abstract  Intramuscular fat content and water-holding capacity are important traits in livestock as they influence meat quality, nutritive value of the muscle, and animal health. As a model for livestock, two inbred lines of the Berlin Muscle Mouse population, which had been long-term selected for high muscle mass, were used to identify genomic regions affecting intramuscular fat content and water-holding capacity. The intramuscular fat content of the Musculus longissimus was on average 1.4 times higher in BMMI806 than in BMMI816 mice. This was accompanied by a 1.5 times lower water-holding capacity of the Musculus quadriceps in BMMI816 mice. Linkage analyses with 332 G3 animals of reciprocal crosses between these two lines revealed quantitative trait loci for intramuscular f... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=5015973 Wed, 06 Jul 2011 06:35:23 +0100 5015973 http://www.medworm.com/index.php?rid=5015975&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj5181424225161p1%2F Abstract  Rat models have been used for many decades to study physiological and pathophysiological mechanisms. Prior to the release of the rat genome and new technologies for targeting gene manipulation, the rat had been the underdog in the genomics era, despite the abundance of physiological data compared to the mouse. The overarching goal of biomedical research is to improve health and advance medical science. Translating human disease gene discovery and validation in the rat, through the use of emerging technologies and integrated tools and databases, is providing power to understand the genetics, environmental influences, and biology of disease. In this review we briefly outline the rat models, bioinformatics tools, and technologies that are changing the landscape of tr... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=5015975 Wed, 06 Jul 2011 06:35:22 +0100 5015975 http://www.medworm.com/index.php?rid=4996756&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj5245h5pq6143372%2F In conclusion, our mapping results indicate that a 3.7-Mb region on chromosome 9 contains a gene that regulates differential response to LPS in 129S1/SvImJ and FVB/NJ strains of mice. Differences in the induction of Casp4 expression by LPS in the two strains suggest that Casp4 is the most likely candidate gene in this region. Content Type Journal ArticlePages 1-12DOI 10.1007/s00335-011-9340-8Authors Ivana V. Yang, Center for Genes, Environment and Health and Department of Medicine, National Jewish Health, 1400 Jackson Street, A650, Denver, CO 80206, USAHolly R. Rutledge, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USAJun Yang, National Institute of Environmental Health Sciences, National Institutes of Health... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=4996756 Thu, 30 Jun 2011 17:49:53 +0100 4996756 http://www.medworm.com/index.php?rid=4990369&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fc5838rv36x652762%2F In this study we combined computational and experimental approaches to identify a FPR3 gene that is controlled by an alternative promoter derived during a SD event. Its transcriptional activity was detected by quantitative reverse transcription polymerase chain reaction. Human alternative transcripts (FPR3-1 and FPR3-2) showed tissue-specific patterns with strong expressions in lung or uterus, while the FPR3-1 transcript of rhesus macaque is broadly expressed in various tissues. Overall, transcriptional variations of FPR3 occur by an alternative promoter during primate evolution. Content Type Journal ArticlePages 1-13DOI 10.1007/s00335-011-9341-7Authors Hong-Seok Ha, Department of Biological Sciences, College of Natural Sciences, Pusan National University, Busan, 609-735 Republic ... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=4990369 Wed, 29 Jun 2011 16:33:33 +0100 4990369 http://www.medworm.com/index.php?rid=4990370&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F7304862270wntx97%2F Abstract  Inflammatory bowel diseases (IBDs) are complex disorders caused by a combination of environmental, microbial, and genetic factors. Genome-wide association studies in humans have successfully identified multiple genes and loci associated with disease susceptibility, but the mechanisms by which these loci interact with each other and/or with environmental factors (i.e., intestinal microbiota) to cause disease are poorly understood. Helicobacter hepaticus-induced intestinal inflammation in mice is an ideal model system for elucidating the genetic basis of IBD susceptibility in a bacterially induced system, as there are significant differences in H. hepaticus-induced disease susceptibility among inbred mouse strains. Infected A/J mice develop acute overexpression of pro... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=4990370 Wed, 29 Jun 2011 15:52:03 +0100 4990370 http://www.medworm.com/index.php?rid=4990371&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F3q62333585201416%2F Abstract  Type 2 diabetes prevalence is increasing worldwide. Treatments are available, but glycaemic control is not always effective in many patients. Better models are needed to create new and improved therapies and to expand our understanding of how type 2 diabetes begins and progresses. Translational research involves the transformation of knowledge from basic scientific discoveries to impacting on public health. This can allow identification of novel molecular mechanisms underlying the disease which can lead to preventative measures, biomarkers for diagnosis, or future therapies. Generation of genetically modified mice has allowed us to investigate the function of genes and develop reproducible models in which the phenotype of the animal can be tested. Mouse models hav... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=4990371 Wed, 29 Jun 2011 05:59:01 +0100 4990371 http://www.medworm.com/index.php?rid=4981264&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F475v1774347645r6%2F Abstract  Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease with no cure. Breakthroughs in understanding ALS pathogenesis came with the discovery of dominant mutations in the superoxide dismutase 1 gene (SOD1) and other genes, including the gene encoding transactivating response element DNA binding protein-43 (TDP-43). This has led to the creation of animal models to further our understanding of the disease and identify a number of ALS-causing mechanisms, including mitochondrial dysfunction, protein misfolding and aggregation, oxidative damage, neuronal excitotoxicity, non-cell autonomous effects and neuroinflammation, axonal transport defects, neurotrophin depletion, effects from extracellular mutant SOD1, and aberrant RNA processing. Here we summarise the... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=4981264 Sun, 26 Jun 2011 05:41:20 +0100 4981264 http://www.medworm.com/index.php?rid=4973893&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F1v32044485l77146%2F The objective of this study was to identify risk loci associated with RLN. To that end we genotyped 234 cases (196 Warmbloods, 20 Trotters, 14 Thoroughbreds, and 4 Draft horses), 228 breed-matched controls, and 69 parents with the Illumina Equine SNP50 BeadChip. Using these data, we quantified population structure and performed single-marker and haplotype-based association studies, as well as family-based linkage analyses. We accounted for population stratification by modeling a random polygenic background effect with covariance structure estimated from genome-wide SNP data. Using the haplotype-based approach, we identified two genome-wide suggestive loci in Warmbloods, respectively on chromosomes 21 (p = 1.62 × 10−6) and 31 (p = 1.69 × 10�... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=4973893 Thu, 23 Jun 2011 06:01:39 +0100 4973893 http://www.medworm.com/index.php?rid=4966370&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fpwq07qk13q65l5r4%2F Abstract  Autoimmune and inflammatory diseases, including type 1 diabetes, multiple sclerosis, inflammatory bowel disease, and rheumatoid arthritis, constitute an important and growing public health burden. However, in many cases our understanding of disease biology is limited and available therapies vary greatly in their efficacy and safety. Animal models of autoimmune and inflammatory diseases have provided valuable tools to researchers investigating their aetiology, pathology, and novel therapeutic strategies. Although such models vary in the degree to which they reflect human autoimmune and inflammatory diseases and caution is required in the extrapolation of animal data to the clinical setting, therapeutic approaches first evaluated in established animal models, includ... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=4966370 Tue, 21 Jun 2011 18:01:19 +0100 4966370 http://www.medworm.com/index.php?rid=4930477&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F95517023x1597ng1%2F Abstract  The defining characteristic of all vertebrates is a spine composed of a regular sequence of vertebrae. In humans, congenital spinal defects occur with an incidence of 0.5–1 per 1,000 live births and arise when the formation of vertebral precursors in the embryo is disrupted. These precursors (somites) form in a process (somitogenesis) in which each somite is progressively separated from an unsegmented precursor tissue. In the past decade the underlying genetic mechanisms driving this complex process have been dissected using animal models, revealing that it requires the coordinated action of at least 300 genes. Deletion of many of these genes in the mouse produces phenotypes with similar vertebral defects to those observed in human congenital abnormalities. This... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=4930477 Sat, 11 Jun 2011 06:32:01 +0100 4930477 http://www.medworm.com/index.php?rid=4930478&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fqm802454p663901k%2F Abstract  Platelets are the small anuclear blood cells that are the product of megakaryocytopoiesis, the process of hematopoietic stem cell commitment to megakaryocyte production and the differentiation and maturation of these cells for platelet release. Deregulation or disruption of megakaryocytopoiesis can result in platelet deficiencies, the thrombocytopenias, with attendant risk of hemorrhage or thrombocytosis, a pathological excess of platelet numbers. Mouse models, particularly those engineered to carry genetic alterations modeling mutations associated with human disease, have provided important insights into megakaryocytopoiesis and deregulation of this process in disease. This review focuses on mouse models of diseases of altered megakaryocyte and platelet number, i... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=4930478 Sat, 11 Jun 2011 06:32:00 +0100 4930478 http://www.medworm.com/index.php?rid=4900157&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F0348pq31527g6881%2F In conclusion, although MITF does not seem to be the causal gene of the QTL initially observed, we do not exclude a prominent role of its transcription and function in the outbreak and evolution of the tumors observed in pigs. Content Type Journal ArticlePages 1-11DOI 10.1007/s00335-011-9334-6Authors Emmanuelle Bourneuf, INRA, UMR Génétique Animale et Biologie Intégrative (GABI), Equipe Génétique Immunité Santé, 78352 Jouy-en-Josas, FranceZhi-Qiang Du, Department of Animal Science and Center for Integrated Animal Genomics, Iowa State University, Ames, IA 50011, USAJordi Estellé, INRA, UMR Génétique Animale et Biologie Intégrative (GABI), Equipe Génétique Immunité Santé, 78352 Jouy-en-Josas, FranceHélène Gilbert, AgroParisTech, UMR GABI, 78352 Jouy-en-Josas, FranceF... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=4900157 Fri, 27 May 2011 18:15:03 +0100 4900157 http://www.medworm.com/index.php?rid=4900158&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F6122016417t37342%2F In this study, however, we describe the first exception to this observation. A reduction of licensed origins due to Mcm4 chaos3 homozygosity reduces active origin density in primary embryonic fibroblasts (MEFs) in a C57BL/6J (B6) background. We found that this is associated with an intrinsically lower level of active origins in this background compared to others. B6 Mcm4 chaos3/chaos3 cells proliferate slowly due to p53-dependent upregulation of p21. In fact, the development of B6 Mcm4 chaos3/chaos3 mice is impaired and a significant fraction of them die at birth. While inactivation of p53 restores proliferation in B6 Mcm4 chaos3/chaos3 MEFs, it paradoxically does not rescue animal lethality. These findings indicate that a reduction of licensed origins may cause a more ... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=4900158 Wed, 25 May 2011 06:18:35 +0100 4900158 http://www.medworm.com/index.php?rid=4851673&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fg122538n74215388%2F Abstract   Mycobacterium avium ssp. paratuberculosis (MAP) infection causes a chronic granulomatous inflammatory condition of the bovine gut that is characterized by diarrhea, progressive weight loss, and emaciation, and ultimately leads to loss in productivity and profitability of dairy operations. The host cytokine machinery is known to play an important role in protecting against MAP infection. Therefore, the goal of the present study was to assess whether polymorphisms in candidate genes encoding important cytokines and cytokine receptors are associated with MAP infection status of dairy cattle. MAP infection status was evaluated based on serum and milk enzyme-linked immunosorbent assays (ELISAs) for MAP-specific antibodies. Twenty previously reported polymorphisms in g... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=4851673 Thu, 19 May 2011 16:36:16 +0100 4851673 http://www.medworm.com/index.php?rid=4818626&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fy564x55p27727177%2F Abstract  Animal models with high predictive power are a prerequisite for translational research. The closer the similarity of a model to Parkinson’s disease (PD), the higher is the predictive value for clinical trials. An ideal PD model should present behavioral signs and pathology that resemble the human disease. The increasing understanding of PD stratification and etiology, however, complicates the choice of adequate animal models for preclinical studies. An ultimate mouse model, relevant to address all PD-related questions, is yet to be developed. However, many of the existing models are useful in answering specific questions. An appropriate model should be chosen after considering both the context of the research and the model properties. This review addresses the v... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=4818626 Wed, 11 May 2011 06:24:19 +0100 4818626 http://www.medworm.com/index.php?rid=4810919&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk6016k21j0217032%2F Abstract  Research on hematological disorders relies on suitable animal models. We retrospectively evaluated the use of the hematological parameters hematocrit (HCT), hemoglobin (HGB), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), mean corpuscular volume (MCV), red blood cell count (RBC), white blood cell count (WBC), and platelet count (PLT) in the phenotype-driven Munich N-ethyl-N-nitrosourea (ENU) mouse mutagenesis project as parameters for the generation of novel animal models for human diseases. The analysis was carried out on more than 16,000 G1 and G3 offspring of chemically mutagenized inbred C3H mice to detect dominant and recessive mutations leading to deviations in the levels of the chosen parameters. Identification of animal... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=4810919 Sat, 07 May 2011 15:42:52 +0100 4810919 http://www.medworm.com/index.php?rid=4787140&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F4174537547860g33%2F In this study we identified a novel Col2a1 missense mutation—c.44406A>C (p.D1469A)—produced by large-scale N-ethyl-N-nitrosourea (ENU) mutagenesis in a mouse line. This mutation was located in the C-propeptide coding region of Col2a1 and in the positions corresponding to a human COL2A1 mutation responsible for platyspondylic lethal skeletal dysplasia, Torrance type (PLSD-T). The phenotype was inherited as a semidominant trait. The heterozygotes were mildly but significantly smaller than wild-type mice. The homozygotes exhibited lethal skeletal dysplasias, including extremely short limbs, severe spondylar dysplasia, severe pelvic hypoplasia, and brachydactyly. As expected, these skeletal defects in the homozygotes were similar to those in PLSD-T patients. The secretion of the muta... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=4787140 Mon, 02 May 2011 15:01:04 +0100 4787140 http://www.medworm.com/index.php?rid=4752115&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F7t70848018t10812%2F Abstract  The inbred rat strains Lewis (LEW) and Spontaneously Hypertensive Rats (SHR) differ with respect to several emotionality- and ethanol intake-related behaviors, one of which (inner locomotion in the open field; OF) is strongly influenced by a locus (Anxrr16) on chromosome (Chr) 4. We aimed to further investigate the influence of Chr 4 on these behaviors and to evaluate the role of the estrous cycle in QTL expression. LEW females and SHR males were intercrossed to produce F1 and F2 rats (96–97/sex), which were then tested in the OF, light–dark box (LDB), forced swimming test (FST), and an ethanol consumption procedure (ECP). In addition, another group of 96 F2 females were tested in the OF and LDB according to their estrous cycle phase. All animals were genotype... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=4752115 Sat, 23 Apr 2011 15:41:34 +0100 4752115 http://www.medworm.com/index.php?rid=4752116&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fl085x21451507hg3%2F Abstract  Skeletal muscle has a remarkable ability to regenerate after repeated and complete destruction of the tissue. The healing phases for an injured muscle undergo an activation program controlled by a dynamically inducible transcriptional regulatory network. Mapping a complex mammalian transcriptional network is confronted by significant challenges and requires the integration of multiple experimental data types. In this work we present a system approach to describe the transcriptional circuitry during skeletal muscle regeneration using time-course expression data and motif scanning information. Time-lagged correlation analysis was utilized to evaluate the transcription factor (TF) → target associations. Our analysis identified six TFs that potentially pla... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=4752116 Thu, 21 Apr 2011 06:10:26 +0100 4752116 http://www.medworm.com/index.php?rid=4744508&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F27u82112w667w277%2F In this study we use functional knockout of PAK-2 and gene replacement with the caspase cleavage-deficient PAK-2D212N mutant to differentiate the biological functions of full-length PAK-2 and caspase-activated PAK-2p34. Knockout of PAK-2 results in embryonic lethality at early stages before organ development, whereas replacement with the caspase cleavage-deficient PAK-2D212N results in viable and healthy mice, indicating that early embryonic lethality is caused by deficiency of full-length PAK-2 rather than lack of caspase activation to the PAK-2p34 fragment. However, deficiency of caspase activation of PAK-2 decreased spontaneous cell death of primary mouse embryonic fibroblasts and increased cell growth at high cell density. In contrast, stress-induced cell death by treatment with ... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=4744508 Sat, 16 Apr 2011 15:56:45 +0100 4744508 http://www.medworm.com/index.php?rid=4708223&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj32v147651437067%2F Abstract  The hush puppy mouse mutant has been shown previously to have skull and outer, middle, and inner ear defects, and an increase in hearing threshold. The fibroblast growth factor receptor 1 (Fgfr1) gene is located in the region of chromosome 8 containing the mutation. Sequencing of the gene in hush puppy heterozygotes revealed a missense mutation in the kinase domain of the protein (W691R). Homozygotes were found to die during development, at approximately embryonic day 8.5, and displayed a phenotype similar to null mutants. Reverse transcription PCR indicated a decrease in Fgfr1 transcript in heterozygotes and homozygotes. Generation of a construct containing the mutation allowed the function of the mutated receptor to be studied. Immunocytochemistry showed that the... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=4708223 Sat, 09 Apr 2011 05:55:51 +0100 4708223 http://www.medworm.com/index.php?rid=4691535&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F78407665q655267v%2F Abstract  The syndrome Multiple Congenital Ocular Anomalies (MCOA) is the collective name ascribed to heritable congenital eye defects in horses. Individuals homozygous for the disease allele (MCOA phenotype) have a wide range of eye anomalies, while heterozygous horses (Cyst phenotype) predominantly have cysts that originate from the temporal ciliary body, iris, and/or peripheral retina. MCOA syndrome is highly prevalent in the Rocky Mountain Horse but the disease is not limited to this breed. Affected horses most often have a Silver coat color; however, a pleiotropic link between these phenotypes is yet to be proven. Locating and possibly isolating these traits would provide invaluable knowledge to scientists and breeders. This would favor maintenance of a desirable coat ... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=4691535 Tue, 05 Apr 2011 09:57:47 +0100 4691535 http://www.medworm.com/index.php?rid=4675218&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F021165244vk61414%2F In this study, we developed 17 intersubspecific subcongenic strains with overlapping and nonoverlapping castaneus regions from the B6.Cg-Pbwg1 congenic strain in order to search for and genetically dissect QTLs affecting body weight into distinct closely linked loci. Phenotypic comparisons of several developed subcongenic strains with the B6 strain revealed that two closely linked but distinct QTLs that regulate body weight, named Pbwg1.11 and Pbwg1.12, are located on an 8.9-Mb region between D2Mit270 and D2Mit472 and on the next 3.6-Mb region between D2Mit205 and D2Mit182, respectively. Further analyses using F2 segregating populations obtained from intercrosses between B6 and each of the two selected subcongenic strains confirmed the presence of these two body weight QTLs. Pbwg1.11 h... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=4675218 Wed, 30 Mar 2011 23:54:09 +0100 4675218 http://www.medworm.com/index.php?rid=4640340&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fn9654v88351r7071%2F Abstract  Malaria continues to be a serious threat to global health. The malaria problem is compounded by the absence of an efficacious vaccine and widespread drug resistance in the Plasmodium malarial parasite. The host factors and parasite virulence determinants that regulate early response to infection and subsequent onset of protective immunity are poorly understood. The molecular characterization of this early host:pathogen interface may identify novel targets for prophylactic or therapeutic intervention. Genetic analyses in mouse model of malaria show that inactivation of the enzyme pantetheinase (Char9 locus) causes susceptibility to blood-stage infection. The pantetheinase product cysteamine is an inexpensive and non-toxic aminothiol that is approved for lifelong cli... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=4640340 Fri, 25 Mar 2011 05:47:40 +0100 4640340 http://www.medworm.com/index.php?rid=4589140&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F13462436215h5016%2F Abstract  Up until late in the third trimester of gestation and through to adulthood, the healing response acts more to regenerate than to repair a wound. The mechanisms underlying this “scar-free” healing remain unknown although the actin cytoskeleton has a major role. Flightless I (Flii), an actin-remodelling protein and essential developmental regulator, negatively affects wound repair but its effect on scar-free fetal healing is unknown. Using fetal skin explants from E17 (regenerate) and E19 (repair) rats, the function of Flii in fetal wound repair was determined. Expression of Flii increased between E17 and E19 days of gestation and wounding transiently increased Flii expression in E17 but not E19 wounds. However, both confocal and immunofluorescent analysis ... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=4589140 Sat, 12 Mar 2011 16:52:04 +0100 4589140 http://www.medworm.com/index.php?rid=4589141&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fq35t330n314v6107%2F Abstract  A comprehensive representation of the gene content of the long arm of human chromosome 21 (Hsa21q) remains of interest for the study of Down syndrome, its associated phenotypic features, and mouse models. Here we compare transcript catalogs for Hsa21q, chimpanzee chromosome 21 (Ptr21q), and orthologous regions of mouse chromosomes 16, 17, and 10 for open reading frame (ORF) characteristics and conservation. The Hsa21q and mouse catalogs contain 552 and 444 gene models, respectively, of which only 162 are highly conserved. Hsa21q transcripts were used to identify orthologous exons in Ptr21q and assemble 533 putative transcripts. Transcript catalogs for all three organisms are searchable for nucleotide and amino acid sequence features of ORF length, repeat content, ... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=4589141 Sat, 12 Mar 2011 16:52:03 +0100 4589141 http://www.medworm.com/index.php?rid=4558355&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F484312n423148047%2F Abstract  Epigenetic inactivation due to aberrant promoter methylation is a key process in breast tumorigenesis. Murine models for human breast cancer have been established for nearly every important human oncogene or tumor suppressor gene. Mouse-to-human comparative gene expression and cytogenetic profiling have been widely investigated for these models; however, little is known about the conservation of epigenetic alterations during tumorigenesis. To determine if this key process in human breast tumorigenesis is also mirrored in a murine breast cancer model, we mapped cytosine methylation changes in primary adenocarcinomas and paired lung metastases derived from the polyomavirus middle T antigen mouse model. Global changes in methylcytosine levels were observed in all tum... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=4558355 Fri, 04 Mar 2011 10:47:16 +0100 4558355 http://www.medworm.com/index.php?rid=4558354&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fc274396262441n43%2F Abstract  Through many different routes of analysis, including human familial studies and animal models, we are identifying an increasing number of genes that are causative for human neurodegenerative disease and are now in a position for many such disorders to dissect the molecular pathology that gives rise to neuronal death. Yet a paradox remains: The majority of the genes identified cause neurodegeneration in specific neuronal subtypes, but the genes themselves are ubiquitously expressed. Furthermore, the different mutations in the same gene may cause quite different types of neurodegeneration. Something in our understanding of neurodegenerative disease is clearly missing, and we refer to this as the phenomenon of “neuronal targeting.” Here we discuss possible explan... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=4558354 Fri, 04 Mar 2011 10:47:16 +0100 4558354 http://www.medworm.com/index.php?rid=4539594&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fpx23381v30rn2768%2F Abstract  Adrenal gland function is mediated through secreted hormones, which play a vital role in the autonomic and hypothalamic-pituitary-adrenal (HPA)-axis-mediated stress response. The genetic underpinnings of the stress response can be approached using a quantitative trait locus (QTL) analysis. This method has been used to investigate genomic regions associated with variation in complex phenotypes, but it has not been used to explore the structure of the adrenal. We used QTL analyses to identify candidate genes underlying adrenal weight and adrenal cortical zone and medulla widths. We used 64 BXD recombinant inbred (RI) strains of mice (n = 528) and 2 parental strains (C57BL/6J and DBA/2J; n = 20) to measure adrenal weights and adrenal zone widths. F... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=4539594 Wed, 23 Feb 2011 23:37:35 +0100 4539594 http://www.medworm.com/index.php?rid=4539595&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F76212p5p854xr814%2F Abstract  An N-ethyl-N-nitrosourea random mutation screen was used to identify recessive modifiers of gene silencing in the mouse using an epigenetically sensitive reporter transgene. One of the mutant lines, MommeR1, was identified as a suppressor of variegation and it showed female-specific age-associated infertility in homozygotes. Linkage analysis identified a region on chromosome 10, containing the Foxo3a gene, previously shown to play a critical role in female gametogenesis. Foxo3a is a transcription factor with roles in cell cycle control, apoptosis, neural and hematopoietic cell differentiation, and DNA repair. Sequencing of the Foxo3a gene in MommeR1 mice revealed a point mutation that causes an amino acid substitution in the highly conserved Forkhead DNA-binding doma... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=4539595 Wed, 23 Feb 2011 23:37:31 +0100 4539595 http://www.medworm.com/index.php?rid=4441538&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fm36824q641824202%2F Content Type Journal ArticlePages 1-8DOI 10.1007/s00335-011-9314-xAuthors Marsha Wallace, Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14850, USAChristopher N. Vlangos, Departments of Pediatrics and Human Genetics, University of Michigan, Ann Arbor, MI 48109, USAElena de la Casa-Esperon, Albacete Science and Technology Park, Regional Center for Biomedical Research (C.R.I.B.), University of Castilla-La Mancha, Albacete, 02006 Spain Journal Mammalian GenomeOnline ISSN 1432-1777Print ISSN 0938-8990 (Source: Mammalian Genome) Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=4441538 Fri, 04 Feb 2011 17:34:21 +0100 4441538 http://www.medworm.com/index.php?rid=4321558&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fp7j17733w5568854%2F Abstract  Variations in diabetic phenotypes are caused by complex interactions of genetic effects, environmental factors, and the interplay between the two. We tease apart these complex interactions by examining genome-wide genetic and epigenetic effects on diabetes-related traits among different sex, diet, and sex-by-diet cohorts in a Mus musculus model. We conducted a genome-wide scan for quantitative trait loci that affect serum glucose and insulin levels and response to glucose stress in an F16 Advanced Intercross Line of the LG/J and SM/J intercross (Wustl:LG,SM-G16). Half of each sibship was fed a high-fat diet and half was fed a relatively low-fat diet. Context-dependent genetic (additive and dominance) and epigenetic (parent-of-origin imprinting) effects were charact... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=4321558 Wed, 05 Jan 2011 16:48:35 +0100 4321558 http://www.medworm.com/index.php?rid=4292139&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fp312975j715x2j01%2F Abstract  This issue of Mammalian Genome explores the genetic approach to infectious disease susceptibility as it has been applied in mammals. Although no single issue of any journal could give comprehensive treatment to a field so extensive and rapidly growing as this one, these texts describe key discoveries that provided new understanding of immune responses. Classical genetic studies opened and continue to pave the way to deep understanding of many issues in immunology. Content Type Journal ArticleDOI 10.1007/s00335-010-9312-4Authors Bruce Beutler, Department of Genetics, The Scripps Research Institute, 10550 North Torrey Pines Road, SP-293, La Jolla, CA 92037, USAChristopher C. Goodnow, John Curtin School of Medical Research, The Australian National University, Bui... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=4292139 Fri, 24 Dec 2010 06:59:26 +0100 4292139 http://www.medworm.com/index.php?rid=4280145&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fm644135157323771%2F In this study, long-bone-length QTL were fine-mapped in the F34 generation (n = 1424) of the LG,SM advanced intercross. Environmental effects were assessed by dividing the population by sex between high-fat and low-fat diets, producing eight sex/diet cohorts. We identified 145 individual bone-length QTL comprising 45 pleiotropic QTL; 69 replicated QTL from previous studies, 35 were new traits significant at previously identified loci, and 41 were novel QTL. Many QTL affected only a subset of the population based on sex and/or diet. Eight of ten known skeletal growth genes were upregulated in 3-week-old LG/J male proximal tibial growth plates relative to SM/J.The sequences of parental strains LG/J and SM/J indicated the presence of over half a million polymorphisms in the con... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=4280145 Mon, 20 Dec 2010 15:19:44 +0100 4280145 http://www.medworm.com/index.php?rid=4274422&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ftu3qv11818161738%2F Abstract  The motor protein myosin IIIA is critical for maintenance of normal hearing. Homozygosity and compound heterozygosity for loss-of-function mutations in MYO3A, which encodes myosin IIIA, are responsible for inherited human progressive hearing loss DFNB30. To further evaluate this hearing loss, we constructed a mouse model, Myo3a KI/KI , that harbors the mutation equivalent to the nonsense allele responsible for the most severe human phenotype. Myo3a KI/KI mice were compared to their wild-type littermates. Myosin IIIA, with a unique N-terminal kinase domain and a C-terminal actin-binding domain, localizes to the tips of stereocilia in wild-type mice but is absent in the mutant. The phenotype of the Myo3a KI/KI mouse parallels the phenotype of human DFNB30. ... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=4274422 Fri, 17 Dec 2010 06:51:26 +0100 4274422 http://www.medworm.com/index.php?rid=4270695&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F601h8x6533312412%2F Abstract  The inner ear consists of the cochlea (the organ of hearing) and the vestibular system (the organs of balance). Within the vestibular system, linear acceleration and gravity are detected by the saccule and utricle. Resting above the neurosensory epithelia of these organs are otoconia, minute proteinaceous and crystalline (calcite) inertial masses that shift under the physical forces imparted by linear movements and gravity. It is the transduction and sensation of these movements and their integration with vision and proprioceptive inputs that contribute to the sensation of balance. It has been proposed that a reactive oxygen species- (ROS-) generating NADPH oxidase comprising the gene products of the Nox3, Noxo1, and Cyba genes plays a critical and constructive rol... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=4270695 Wed, 15 Dec 2010 19:11:08 +0100 4270695 http://www.medworm.com/index.php?rid=4240689&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F1u1282u85671734k%2F In this study the six SNPs ALGA0072075, ALGA0106330, MUC13-226, MUC13-813, DIA0000584, and MARC0006918 were in complete linkage disequilibrium with F4bcR. Based on this finding and earlier investigations, we suggest that the locus for F4bcR is located between the LMLN locus and microsatellite S0283. Content Type Journal ArticleDOI 10.1007/s00335-010-9305-3Authors Antonio Rampoldi, Institute of Plant, Animal and Agroecosystem Sciences, ETH Zurich, 8092 Zurich, SwitzerlandMette J. Jacobsen, Basic Animal and Veterinary Sciences, University of Copenhagen, 1870 Frederiksberg, Copenhagen, DenmarkHans U. Bertschinger, Institute of Plant, Animal and Agroecosystem Sciences, ETH Zurich, 8092 Zurich, SwitzerlandDavid Joller, Institute of Plant, Animal and Agroecosystem Sciences, ETH Zurich, 80... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=4240689 Mon, 06 Dec 2010 18:44:37 +0100 4240689 http://www.medworm.com/index.php?rid=4229901&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ffr425p5315023716%2F Abstract  The leptin receptor (LEPR) is a key gene in the control of food intake and energy homeostasis. The sequence variant LEPR{NM_001024587.1}:c.1987C>T has been associated with growth, fatness, and body composition in several pig populations. The purpose of this work was to confirm the phenotypic effects of this SNP in two new experimental backcrosses involving Iberian, Landrace, and Duroc breeds, and to evaluate the quantitative effects of the SNP on the hypothalamic expression of LEPR and two other downstream genes. Results indicate significant additive effects of the SNP on body weight, back fat thickness, and hypothalamic LEPR gene expression in both populations. Allele T fixed in the Iberian breed is systematically associated with a higher growth and fat depositio... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=4229901 Thu, 02 Dec 2010 18:07:14 +0100 4229901 http://www.medworm.com/index.php?rid=4229902&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F5kw51571635q67t6%2F We report an initial analysis of copy number variations (CNVs) in cattle selected for resistance or susceptibility to intestinal nematodes. We performed three array comparative genomic hybridization (CGH) experiments to compare Angus cattle with extreme phenotypes for fecal egg count and serum pepsinogen level. We identified 20 CNVs in total, of which 12 were within known chromosomes harboring or adjacent to gains or losses. About 85% of the CNV identified (17/20) overlapped with cattle CNV regions that were reported recently. Selected CNVs were further validated by independent methods using quantitative PCR (qPCR) and FISH. Pathway analyses indicated that annotated cattle genes within these variable regions are particularly enriched for immune function affecting receptor activities... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=4229902 Thu, 02 Dec 2010 06:49:01 +0100 4229902 http://www.medworm.com/index.php?rid=4228126&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fh824n72666m0l635%2F Abstract  Malaria is a disease that infects over 500 million people, causing at least 1 million deaths every year, with the majority occurring in developing countries. The current antimalarial arsenal is becoming dulled due to the rapid rate of resistance of the parasite. However, in populations living in malaria-endemic regions there are many examples of genetic-based resistance to the severe effects of the parasite Plasmodium. Defining the genetic factors behind host resistance has been an area of great scientific interest over the last few decades; this review summarizes the current knowledge of the genetic loci involved. Perhaps the lessons learned from the natural variation in both the human populations and experimental mouse models of infection may pave the way for nov... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=4228126 Tue, 30 Nov 2010 06:58:16 +0100 4228126 http://www.medworm.com/index.php?rid=4228127&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F1635k86527u1g025%2F Abstract  Progeny from the Harwell N-ethyl-N-nitrosourea (ENU) recessive mutagenesis screen were assessed for auditory defects. A pedigree was identified with multiple progeny lacking response to a clickbox test. Auditory brainstem response (ABR) analysis showed that homozygous mutant mice were profoundly deaf and the line was named melody. We subsequently mapped this mutation to a 6-Mb region on chromosome 8 and identified a point mutation in melody that results in a C163S substitution in the catalytic site of Caspase 3, a cysteine protease involved in apoptosis. Melody fails to complement a null Caspase-3 mutant. Scanning electron microscopy (SEM) has revealed disorganised sensory hair cells and hair cell loss. Histological analysis of melody has shown degeneration of spiral... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=4228127 Tue, 30 Nov 2010 06:58:12 +0100 4228127 http://www.medworm.com/index.php?rid=4207009&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F313213x5h4755w7l%2F Abstract  Recent linkage-based studies in humans suggest the presence of loci that affect either genome-wide recombination rates, utilization of recombination hotspots, or both. We have been interested in utilizing cytological methodology to directly assess recombination in mammalian meiocytes and to identify recombination-associated loci. In the present report we summarize studies in which we combined a cytological assay of recombination in mouse pachytene spermatocytes with QTL analyses to identify loci that contribute to genome-wide levels of recombination in male meiosis. Specifically, we analyzed MLH1 foci, a marker of crossovers, in 194 F2 male mice derived from a subspecific cross between CAST/EiJ and C57BL/6J parental strains. We then used these data to uncover loci... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=4207009 Fri, 26 Nov 2010 18:04:37 +0100 4207009 http://www.medworm.com/index.php?rid=4207010&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F4v83101645558872%2F Abstract  The Ts65Dn mouse is trisomic for orthologs of about half the genes on Hsa21. A number of phenotypes in these trisomic mice parallel those in humans with trisomy 21 (Down syndrome), including cognitive deficits due to hippocampal malfunction that are sufficiently similar to human that “therapies” developed in Ts65Dn mice are making their way to human clinical trials. However, the impact of the model is limited by availability. Ts65Dn cannot be completely inbred and males are generally considered to be sterile. Females have few, small litters and they exhibit poor care of offspring, frequently abandoning entire litters. Here we report identification and selective breeding of rare fertile males from two working colonies of Ts65Dn mice. Trisomic offspring can be p... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=4207010 Thu, 25 Nov 2010 20:06:03 +0100 4207010 http://www.medworm.com/index.php?rid=4202254&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fh7817v61nmprg774%2F In this study we carried out manipulation of regulatory elements of the endogenous gene in mice and extensive transgenic analysis of the Tbx1 locus. Results indicated that the Fox binding site is dispensable for Tbx1 gene expression, but the enhancer within which it is located regulates, to a limited extent, mesodermal expression of the gene. Transgenic analysis of conserved noncoding regions within 54 kb of the Tbx1 locus identified a novel pharyngeal endoderm-specific enhancer and an intronic suppressor element. Overall, our data suggest a regulatory architecture of the Tbx1 gene made of tissue-specific modules and redundant elements that individually contribute, to a modest extent, to the expression of the gene. Content Type Journal ArticleDOI 10.1007/s00335-010-9304-4Auth... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=4202254 Wed, 24 Nov 2010 18:50:43 +0100 4202254 http://www.medworm.com/index.php?rid=4202255&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F1118l70730261m62%2F Abstract  Otitis media (OM) is among the most common illnesses of early childhood, characterised by the presence of inflammation in the middle ear cavity. Acute OM and chronic OM with effusion (COME) affect the majority of children by school age and have heritability estimates of 40–70%. However, the majority of genes underlying this susceptibility are, as yet, unidentified. One method of identifying genes and pathways that may contribute to OM susceptibility is to look at mouse mutants displaying a comparable phenotype. Single-gene mouse mutants with OM have identified a number of genes, namely, Eya4, Tlr4, p73, MyD88, Fas, E2f4, Plg, Fbxo11, and Evi1, as potential and biologically relevant candidates for human disease. Recent studies suggest that this “mouse-to-human”... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=4202255 Wed, 24 Nov 2010 18:50:42 +0100 4202255 http://www.medworm.com/index.php?rid=4199475&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fht47513uk1814272%2F Abstract  Several studies have suggested a role for human genetic risk factors in the susceptibility to developing tuberculosis (TB). However, results of these studies have been inconsistent, and one potential reason for these inconsistencies is variation in aspects of study design. Specifically, phenotype definitions and population genetic factors have varied dramatically. Since TB is a complex trait, there are many challenges in designing studies to assess appropriately human genetic risk factors for the development of TB as opposed to the acquisition of latent M. tuberculosis infection. In this review we summarize these important study design differences, with illustrations from the TB genetics literature. We cite specific examples of studies of the NRAMP1 (SLC11A1) gene ... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=4199475 Mon, 22 Nov 2010 16:43:57 +0100 4199475 http://www.medworm.com/index.php?rid=4178057&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F4115v84w257w35t4%2F The objective of this study was to determine the feasibility of using cDNA microarray and quantitative real-time PCR (qRT-PCR) analysis to determine gene expression patterns in metastatic versus nonmetastatic canine STSs, given the inherent heterogeneity of this group of tumors. Five STSs from dogs with metastatic disease were evaluated in comparison to eight STSs from dogs without metastasis. Tumor RNA was extracted, processed, and labeled for application to the Affymetrix Canine Genechip 2.0 Array. Array fluorescence was normalized using D-Chip software and data analysis was performed with JMP/Genomics. Differential gene expression was validated using qRT-PCR. Over 200 genes were differentially expressed at a false discovery rate of 5%. Differential gene expression was validated fo... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=4178057 Sat, 13 Nov 2010 06:45:10 +0100 4178057 http://www.medworm.com/index.php?rid=4161682&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fl15551r03545t0nq%2F Abstract  Mn superoxide dismutase (MnSOD)-deficient mice (Sod2−/−) suffer from mitochondrial damage and have various survival times and phenotypic presentations that are dependent on the genetic background of the mutant mice. The mitochondrial NADPH transhydrogenase (NNT) was identified as a putative genetic modifier based on a genome-wide quantitative trait association study on the molecular defect of the protein in more severely affected Sod2−/− mice and on the biological function of NNT. Hence, Sod2−/− mice on the C57BL/6J (B6J) background have the shortest survival time, and the mice are homozygous for the truncated Nnt allele (Nnt T ). On the other hand, genetic backgrounds that support longer survival of Sod2−/− mice all have at least one normal copy ... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=4161682 Wed, 10 Nov 2010 17:23:02 +0100 4161682 http://www.medworm.com/index.php?rid=4148731&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F8x7222m5k23502kk%2F This study creates guidelines to maximize the accuracy of SNP discovery and prevention of false-positive SNP detection, and provides more than 33,000 SNPs located in coding regions of genes expressed during lactation that can be used to develop genotyping platforms to perform marker-trait association studies in Holstein cattle. Content Type Journal ArticleDOI 10.1007/s00335-010-9297-zAuthors Angela Cánovas, IRTA, Genètica i Millora Animal, 191 Alcalde Rovira Roure Av, 25198 Lleida, SpainGonzalo Rincon, Department of Animal Science, University of California-Davis, One Shields Ave, Davis, 95616 CA USAAlma Islas-Trejo, Department of Animal Science, University of California-Davis, One Shields Ave, Davis, 95616 CA USASaumya Wickramasinghe, Department of Animal Science, University of... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=4148731 Sat, 06 Nov 2010 20:16:49 +0100 4148731 http://www.medworm.com/index.php?rid=4142135&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F5472150608315652%2F Abstract  The innate immune responses mediated by Toll-like receptors (TLR) provide an evolutionarily well-conserved first line of defense against microbial pathogens. In the Reactome Knowledgebase we previously integrated annotations of human TLR molecular functions with those of over 4000 other human proteins involved in processes such as adaptive immunity, DNA replication, signaling, and intermediary metabolism, and have linked these annotations to external resources, including PubMed, UniProt, EntrezGene, Ensembl, and the Gene Ontology to generate a resource suitable for data mining, pathway analysis, and other systems biology approaches. We have now used a combination of manual expert curation and computer-based orthology analysis to generate a set of annotations for T... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=4142135 Thu, 04 Nov 2010 17:47:10 +0100 4142135 http://www.medworm.com/index.php?rid=4142136&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fl1u1k71612944320%2F Abstract  The immunity-related GTPases (IRGs) belong to the family of large, interferon-inducible GTPases and constitute a cell-autonomous resistance system essential for the control of vacuolar pathogens like Toxoplasma gondii in mice. Recent results demonstrated that numerous IRG members accumulate collaboratively at the parasitophorous vacuole of invading T. gondii leading to the destruction of the vacuole and the parasite and subsequent necrotic host cell death. Complex regulatory interactions between different IRG proteins are necessary for these processes. Disturbance of this finely balanced system, e.g., by single genetic deficiency for the important negative regulator Irgm1 or the autophagic regulator Atg5, leads to spontaneous activation of the effector IRG proteins... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=4142136 Thu, 04 Nov 2010 17:47:08 +0100 4142136 http://www.medworm.com/index.php?rid=4094486&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fwq83260m2201481n%2F Abstract  Agenesis of the corpus callosum (ACC) is a congenital abnormality of the brain structure. We have produced transgenic mice expressing both reverse tetracycline-controlled transactivator (rtTA) and transcriptional silencer (tTS) ubiquitously. Although the transgene products do not affect development of the mouse brain, one of the founder lines, TAS, showed ACC, suggesting transgenic disruption of endogenous gene(s). To identify the causative gene and its role in ACC, we performed pathological investigations of the brain and chromosomal mapping of foreign genes in TAS mice. Sixty-two percent of the heterozygous TAS mice showed ACC accompanied with formation of Probst bundles, as seen in human. Complete penetrance of ACC was observed in homozygous TAS mice. Furthermo... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=4094486 Thu, 21 Oct 2010 17:14:37 +0100 4094486 http://www.medworm.com/index.php?rid=4094487&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fqj6q8713807487pq%2F Abstract  Using genome-wide mutagenesis with N-ethyl-N-nitrosourea (ENU), a mouse mutant with cryptorchidism was identified. Genome mapping and exon sequencing identified a novel missense mutation (D294G) in Relaxin/insulin-like family peptide receptor 2 (Rxfp2). The mutation impaired testicular descent and resulted in decreased testis weight in Rxfp2 DG/DG mice compared to Rxfp2 +/DG and Rxfp2 +/+ mice. Testicular histology of the Rxfp2 DG/DG mice revealed spermatogenic defects ranging from germ cell loss to tubules with Sertoli-cell-only features. Genetic complementation analysis using a loss-of-function allele (Rxfp2 −) confirmed causality of the D294G mutation. Specifically, mice with one of each mutant allele (Rxfp2 DG/−) exhibited decreased testis weigh... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=4094487 Thu, 21 Oct 2010 05:53:28 +0100 4094487 http://www.medworm.com/index.php?rid=4094488&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fyk0247n75k5r2hmn%2F Abstract  Major Histocompatibility Complex (MHC) genes play a key role in immune response to infectious diseases, immunosurveillance, and self/nonself recognition. Matching MHC alleles is critical for organ transplantation, while changes in the MHC profile of tumour cells allow effective evasion of the immune response. Two unique cancers have exploited these features to become transmissible. In this review I discuss the functional role of MHC molecules in the emergence and evolution of Devil Facial Tumour Disease (DFTD) and Canine Transmissible Venereal Tumour (CTVT). High levels of genetic diversity at MHC genes play a critical role in protecting populations of vertebrate species from contagious cancer. However, species that have undergone genetic bottlenecks and have lost... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=4094488 Wed, 20 Oct 2010 17:53:23 +0100 4094488 http://www.medworm.com/index.php?rid=4084887&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fc8h6817816302pr7%2F Abstract  Hair is a unique structure, characteristic of mammals, controlling body homeostasis, as well as cell and tissue integration. Previous studies in dog, mouse, and rat have identified polymorphisms in Keratin 71 (KRT71) as responsible for the curly/wavy phenotypes. The coding sequence and the 3′ UTR of KRT71 were directly sequenced in randomly bred and pedigreed domestic cats with different pelage mutations, including hairless varieties. A SNP altering a splice site was identified in the Sphynx breed and suggested to be the hairless (hr) allele, and a complex sequence alteration, also causing a splice variation, was identified in the Devon Rex breed and suggested to be the curly (re) allele. The polymorphisms were genotyped in approximately 200 cats. All the Devon Rex... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=4084887 Sat, 16 Oct 2010 07:48:19 +0100 4084887 http://www.medworm.com/index.php?rid=4052806&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fr6lj286877hp6461%2F Abstract  Leprosy (Hansen’s disease) is a human infectious disease whose etiological agent, Mycobacterium leprae, was identified by G. H. A. Hansen in the 19th century. Despite the high efficacy of multidrug therapy (<0.1% annual relapse rate), transmission is persistent. In 2008, approximately 250,000 new cases were reported to the World Health Organization. Clinically, leprosy presents as either the paucibacillary (1–5 lesions) or the multibacillary (>5 lesions) subtype, highly reflective of a Th1 (cell-mediated) or Th2 (humoral) host immune response, respectively. Subsequent to Mycobacterium leprae exposure, epidemiological studies (e.g., twin studies and complex segregation analyses) maintain the importance of host genetics in susceptibility to leprosy. The resu... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=4052806 Fri, 08 Oct 2010 17:02:56 +0100 4052806 http://www.medworm.com/index.php?rid=4052808&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F3u444727545g5463%2F This article describes a new nomenclature system for human, mouse, and rat carboxylesterase genes that identifies homolog gene families and allocates a unique name for each gene. The guidelines of human, mouse, and rat gene nomenclature committees were followed and “CES” (human) and “Ces” (mouse and rat) root symbols were used followed by the family number (e.g., human CES1). Where multiple genes were identified for a family or where a clash occurred with an existing gene name, a letter was added (e.g., human CES4A; mouse and rat Ces1a) that reflected gene relatedness among rodent species (e.g., mouse and rat Ces1a). Pseudogenes were named by adding “P” and a number to the human gene name (e.g., human CES1P1) or by using a new letter followed by ps for mouse and rat Ces pseu... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=4052808 Thu, 07 Oct 2010 16:48:42 +0100 4052808 http://www.medworm.com/index.php?rid=4052807&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F32268l4261p61766%2F Abstract  There are multiple theories on the evolution of genomic imprinting. We investigated whether the molecular evolution of true orthologs of known imprinted genes provides support for theories based on gene duplication or parental conflicts (where mediated by amino-acid changes). Our analysis of 34 orthologous genes demonstrates that the vast majority of mammalian imprinted genes have not undergone any subsequent significant gene duplication within placental species, suggesting that selection pressures against gene duplication events could be operating for imprinted loci. As antagonistic co-evolution between imprinted genes can regulate offspring growth, proteins mediating this interaction could be subject to rapid evolution via positive selection. Supporting this, we... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=4052807 Thu, 07 Oct 2010 16:48:42 +0100 4052807 http://www.medworm.com/index.php?rid=4026610&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fl4716ut6v45p823q%2F This study aimed to clarify the genetic basis of strain differences in the temporal pattern of home-cage activity between MSM and B6. Through the comparison of temporal patterns of home-cage activity between B6 and MSM, the pattern can be classified into five temporal components: (1) resting phase, (2) anticipation phase, (3) 1st phase, (4) 2nd phase, and (5) 3rd phase. To identify quantitative trait loci (QTLs) involved in these temporal components, we used consomic strains established from crosses between B6 and MSM. Five consomic strains, for Chrs 2T (telomere), 3, 4, 13, and 14, showed significantly higher total activity than B6. In contrast, the consomic strains of Chrs 6C (centromere), 7T, 9, 11, and 15 were less active than B6. This indicates that multigenic factors regulate ... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=4026610 Fri, 01 Oct 2010 07:13:26 +0100 4026610 http://www.medworm.com/index.php?rid=4026611&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F4l86v21661k8k526%2F Abstract  The adenomatous polyposis coli (APC) gene is known to act as a tumor suppressor gene in both sporadic and hereditary colorectal cancer by negatively regulating WNT signaling. Familial adenomatous polyposis (FAP) patients develop intestinal polyps due to the presence of a single germline mutation in APC. The severity of the FAP phenotype is a function of the position of the APC mutation, indicating a complex role for APC that extends beyond the canonical WNT pathway. APC encodes a large protein with multiple functional domains, including an armadillo repeat domain that has been linked to protein–protein interactions. To determine the effect of the armadillo repeat domain on intestinal tumorigenesis, we generated a congenic mouse line (Apc Δ242 ) carrying a gen... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=4026611 Fri, 01 Oct 2010 07:13:25 +0100 4026611 http://www.medworm.com/index.php?rid=4024936&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F037318n7273n0497%2F Abstract  Cytomegaloviruses (CMV) are ubiquitous, opportunistic DNA viruses that have mastered the art of immune evasion through their ability to mimic host proteins or to inhibit antiviral responses. The study of the host response against CMV infection has illuminated many facets of the complex interaction between host and pathogen. Here, we review evidence derived from the animal models and human studies that supports the central role played by innate immune receptors in the recognition of virus infection and their participation in the many layers of defense. Content Type Journal ArticleDOI 10.1007/s00335-010-9286-2Authors Michal Pyzik, Department of Human Genetics and Centre for the Study of Host Resistance, McGill University, Montreal, QC H3G 0B1, CanadaEve-Marie G... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=4024936 Thu, 30 Sep 2010 08:16:33 +0100 4024936 http://www.medworm.com/index.php?rid=4021529&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fhkt9260l87238677%2F Abstract  Insulin resistance and altered endocrine pancreas function are central pathophysiological features of type 2 diabetes mellitus (T2DM). The Goto-Kakizaki (GK) rat is a model of spontaneous T2DM characterised by reduced beta cell mass and genetically determined glucose intolerance and altered insulin secretion. To identify genetic determinants of endocrine pancreas histopathology, we carried out quantitative trait locus (QTL) mapping of histological phenotypes (beta cell mass -BCM and insulin-positive cell area -IPCA) and plasma concentration of hormones and growth factors in a F2 cohort derived from GK and normoglycemic Brown Norway rats. Although IPCA and BCM in the duodenal region of the pancreas were highly positively correlated (P < 10−6), and sim... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=4021529 Tue, 28 Sep 2010 19:14:26 +0100 4021529 http://www.medworm.com/index.php?rid=4010262&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F73rnp2860824448n%2F Abstract  The oculocerebrorenal syndrome of Lowe (OCRL; MIM #309000) is an X-linked human disorder characterized by congenital cataracts, mental retardation, and renal proximal tubular dysfunction caused by loss-of-function mutations in the OCRL gene that encodes Ocrl, a type II phosphatidylinositol bisphosphate (PtdIns4,5P2) 5-phosphatase. In contrast, mice with complete loss-of-function of the highly homologous ortholog Ocrl have no detectable renal, ophthalmological, or central nervous system abnormalities. We inferred that the disparate phenotype between Ocrl-deficient humans and mice was likely due to differences in how the two species compensate for loss of the Ocrl enzyme. We therefore turned our attention to Inpp5b, another type II PtdIns4,5P2 5-phosphatase encoded by ... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=4010262 Sat, 25 Sep 2010 16:57:48 +0100 4010262 http://www.medworm.com/index.php?rid=3991720&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fbl571784k41627mn%2F Abstract  Kallikrein-related peptidases (KLKs) constitute a major family of proteolytic enzymes implicated in the pathogenesis of many diseases, including cancer. Recently, we have suggested that the dog might represent a useful animal model for in vivo KLK studies and sought to investigate the expression patterns of the largely unknown canine KLK family. Along the same lines, in the present report we experimentally characterized five previously unidentified (CANFA)KLKs and investigated their expression in normal and tumorous mammary tissues. We demonstrated that the GenBank sequences that were predicted in silico to represent the canine orthologs of human KLK5, KLK6, KLK7, and KLK8 mRNAs were correct, whereas the one corresponding to the canine KLK4 had a major inconsistency ... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=3991720 Sun, 19 Sep 2010 05:57:00 +0100 3991720 http://www.medworm.com/index.php?rid=3912807&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fc583k548262q5g3r%2F This study enabled us to test the theory that disease outcome may be due to interaction of several gene effects. With eight instances of statistically significant gene-gene interactions, the importance of epistasis is clearly identifiable in this study. Methods for studying gene-gene interactions are based on a multilocus and multigene approach, consistent with the nature of complex-trait diseases, and may provide the paradigm for future genetic studies of TB. Content Type Journal ArticleDOI 10.1007/s00335-010-9280-8Authors Erika de Wit, Molecular Biology and Human Genetics, MRC Centre for Molecular and Cellular Biology and the DST/NRF Centre of Excellence for Biomedical TB Research, Faculty of Health Sciences, Stellenbosch University, PO Box 19063, Tygerberg, 7505 South AfricaL... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=3912807 Thu, 26 Aug 2010 18:10:22 +0100 3912807 http://www.medworm.com/index.php?rid=3912808&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F44t72416p6516gr7%2F This study uses the example of the noninvasive blood pressure test to demonstrate how statistical investigation is important for generating meaningful, reliable results and assessing the design for the defined research objectives. The analysis adjusts for the multiple-testing problem by applying the false discovery rate, which controls the number of false calls within those highlighted as significant. A variance analysis finds that the variation between mice dominates this assay. These variance measures were used to examine the interplay between days, readings, and number of mice on power, the ability to detect change. If an experiment is underpowered, we cannot conclude whether failure to detect a biological difference arises from low power or lack of a distinct phenotype, hence th... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=3912808 Thu, 26 Aug 2010 18:10:21 +0100 3912808 http://www.medworm.com/index.php?rid=3866569&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fgg0627rt37201701%2F The objective of this study was to identify modest-effect genes associated with Mycobacterium avium subsp. paratuberculosis (Map) tissue infection or fecal shedding using GSEA-SNP applied to KEGG pathways or Gene Ontology (GO) gene sets. The Illumina Bovine SNP50 BeadChip was used to genotype 209 Holstein cows for the GSEA-SNP analyses. For each of 13,744 annotated genes genome-wide located within 50 kb of a Bovine SNP50 SNP, the single SNP with the highest Cochran-Armitage Max statistic was used as a proxy statistic for that gene’s strength of affiliation with Map. Gene-set enrichment was tested using a weighted Kolmogorov-Smirnov-like running sum statistic with data permutation to adjust for multiple testing. For tissue infection and fecal shedding, no gene sets in KEGG pathw... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=3866569 Thu, 12 Aug 2010 19:50:14 +0100 3866569 http://www.medworm.com/index.php?rid=3866570&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F7202618128386kw5%2F The objective of this study was to determine whether any of these genes in the syntenic region are likely candidates as modifiers for clot stability. Seven genes, Twsg1, Zfp161, Dlgap1, Ralbp1, Myom1, Rab31, and Emilin2, of the 23 genes with single nucleotide polymorphisms (SNPs) in the mRNA-UTR had differential expression in B6 and A/J mice. Dlgap1, Ralbp1, Myom1, and Emilin2 also had nonsynonymous SNPs. In addition, two other genes had nonsynonymous SNPs, Lama1 and Ndc80. Of these nine candidate genes, Emilin2 was selected for further analysis since other EMILIN (Elastin Microfibril Interface Located Protein) proteins have known functions in vascular structure and coagulation. Differences were found between B6 and A/J mice in vessel wall architecture and EMILIN2 protein in plasma, ca... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=3866570 Wed, 11 Aug 2010 06:37:26 +0100 3866570 http://www.medworm.com/index.php?rid=3866571&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fm7v67w438t435461%2F Abstract  The clinical relevance of fungal infections has increased dramatically in recent decades as a consequence of the rise of immunocompromised populations, and efforts to understand the underlying mechanisms of protective immunity have attracted renewed interest. Here we review Dectin-1, a pattern recognition receptor involved in antifungal immunity, and discuss recent discoveries of polymorphisms in the gene encoding this receptor which result in human disease. Content Type Journal ArticleDOI 10.1007/s00335-010-9277-3Authors Mohlopheni J. Marakalala, Institute of Infectious Diseases and Molecular Medicine, Division of Immunology, CLS, University of Cape Town, Cape Town, 7925 South AfricaAnn M. Kerrigan, Aberdeen Fungal Group, Section of Immunology and Infection, ... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=3866571 Wed, 11 Aug 2010 06:35:46 +0100 3866571 http://www.medworm.com/index.php?rid=3830424&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fr11l4h7737m31866%2F Abstract  To date around 140 genetic alleles have been identified as being responsible for mouse cataract pathology, including Crya, Cryb, Cryg, Maf, Pax6, Pitx3, Sox, Connexins, MIP, and Lim-2. We obtained a dominant cataract mouse model from a spontaneous mutation in the F1 hybrids of outbred strain ICR mice crossed to the inbred strain BALB/cJ mice. Heterozygous and homozygous mutants expressed a nuclear cataract in both eyes. In 8-day-old mice, histological analysis showed that polygon epithelial cells were in the equatorial region and cortex underneath, and vacuole and sponge-like degeneration were in the cortical area underneath the posterior lens capsule. The nucleus of the lens was a deeply stained pink, with the shorter fibers losing their normal arrangement. For the... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=3830424 Thu, 05 Aug 2010 13:25:09 +0100 3830424 http://www.medworm.com/index.php?rid=3830423&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fa5gj0815k76g23w3%2F Abstract  Oculoskeletal dysplasia segregates as an autosomal recessive trait in the Labrador retriever and Samoyed canine breeds, in which the causative loci have been termed drd1 and drd2, respectively. Affected dogs exhibit short-limbed dwarfism and severe ocular defects. The disease phenotype resembles human hereditary arthro-ophthalmopathies such as Stickler and Marshall syndromes, although these disorders are usually dominant. Linkage studies mapped drd1 to canine chromosome 24 and drd2 to canine chromosome 15. Positional candidate gene analysis then led to the identification of a 1-base insertional mutation in exon 1 of COL9A3 that cosegregates with drd1 and a 1,267-bp deletion mutation in the 5′ end of COL9A2 that cosegregates with drd2. Both mutations affect the COL... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=3830423 Thu, 05 Aug 2010 13:25:09 +0100 3830423 http://www.medworm.com/index.php?rid=3785825&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fl97xm271759264u6%2F Abstract  Mitochondria are dynamic cellular organelles that balance fission and fusion to regulate organelle morphology, distribution, and activity, and Opa1 is one of three GTPases known to regulate mitochondrial fusion. In humans, loss of a single Opa1 allele causes dominant optic atrophy, a degenerative condition that leads to loss of vision. Here we demonstrate that the lilR3 mutant mouse phenotype is due to a point mutation in the Opa1 gene resulting in mislocalized Opa1 protein from the mitochondria to the cytosol. Importantly, the mutation is in the middle domain of the Opa1 protein, for which no function had been described. Lack of mitochondrial retention of Opa1 is sufficient to cause the cellular Opa1 loss-of-function phenotype as the mitochondria are fragmented, in... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=3785825 Fri, 23 Jul 2010 12:23:25 +0100 3785825 http://www.medworm.com/index.php?rid=3749224&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F3112g41070628855%2F Abstract  The mouse is an irreplaceable model for understanding the precise genetic mechanisms of mammalian physiological pathways. Thousands of quantitative trait loci (QTLs) have been mapped onto the mouse genome during the last two decades. However, only a few genes’ underlying complex traits have been successfully identified, and rapid fine mapping of QTL genes still remains a challenge for mouse geneticists. Currently, the Collaborative Cross (CC) has proceeded to the goal of establishing more than 1,000 recombinant inbred strains for the sub-centimorgan mapping resolution of QTL loci. In this article, a novel complementary strategy, designated as population of specific chromosome substitution strains or PSCSS, is proposed for rapid fine mapping of QTLs on the substi... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=3749224 Sun, 11 Jul 2010 12:14:00 +0100 3749224 http://www.medworm.com/index.php?rid=3749223&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F327j835482vw3261%2F Abstract  The first scientific meeting of the newly established European SYSGENET network took place at the Helmholtz Centre for Infection Research (HZI) in Braunschweig, April 7-9, 2010. About 50 researchers working in the field of systems genetics using mouse genetic reference populations (GRP) participated in the meeting and exchanged their results, phenotyping approaches, and data analysis tools for studying systems genetics. In addition, the future of GRP resources and phenotyping in Europe was discussed. Content Type Journal ArticleDOI 10.1007/s00335-010-9273-7Authors Klaus Schughart, Helmholtz Centre for Infection Research Department of Infection Genetics 38124 Braunschweig GermanySYSGENET consortium Journal Mammalian GenomeOnline ISSN 1432-1777Print ISSN ... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=3749223 Sun, 11 Jul 2010 12:14:00 +0100 3749223 http://www.medworm.com/index.php?rid=3701421&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F597g118k375u661k%2F Abstract  Meiotic silencing of unsynapsed chromatin (MSUC) occurs in the germ cells of translocation carriers and may cause meiotic arrest and infertility. We hypothesized that if bypassing meiotic checkpoints MSUC may cause epigenetic defects in sperm. We investigated the meiotic behavior of the Robertsonian translocation Rb (8.12) in mice. The unsynapsed 8 and 12 trivalent was associated with the XY body during early and mid-pachynema in heterozygous Rb (8.12) carriers, suggesting possible silencing of pericentromeric genes, such as the Dnmt3a gene. In wild-type mice, DNMT3A protein showed a dramatic accumulation in the nucleus during the mid-pachytene stage and distinct association with the XY body. In translocation carriers, DNMT3A was less abundant in a proportion of pa... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=3701421 Fri, 25 Jun 2010 16:51:57 +0100 3701421 http://www.medworm.com/index.php?rid=3694312&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F52j2vn8031783x04%2F Abstract  The aim of the present study was to detect quantitative trait loci (QTL) for innate and adaptive immunity in pigs. For this purpose, a Duroc × Pietrain F2 resource population (DUPI) with 319 offspring was used to map QTL for the immune traits blood antibodies and interferon-gamma using 122 microsatellites covering all autosomes. Antibodies response to Mycoplasma hyopneumoniae and tetanus toxoid vaccine and the interferon-gamma (IFNG) serum concentration were measured at three different time points and were used as phenotypes. The differences of antibodies and interferon concentration between different time points were also used for the linkage mapping. Line-cross and imprinting QTL analysis, including two-QTL, were performed using QTL Express. A total of... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=3694312 Tue, 22 Jun 2010 14:34:35 +0100 3694312 http://www.medworm.com/index.php?rid=3670144&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fwu201213g1583k3g%2F Abstract   USP32, on chromosomal band 17q23.1-17q23.2, is a highly conserved but uncharacterized gene that gave rise during evolution to a well-known hominoid-specific proto-oncogene, USP6. We investigated the expression profile of USP32 in human tissues and examined its functions to gain insight into this novel member of the well-conserved ubiquitination system. We detected ubiquitous USP32 expression across tissues and confirmed the predicted deubiquitination function owing to the presence of conserved peptidase signature aspargine, cysteine, histidine, and aspartic acid domains of ubiquitin-specific proteases. A Golgi localization of GFP-fused USP32 was detected by fluorescent protection assay and BODIPY-TR staining. In addition, stable silencing of USP32 caused a signifi... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=3670144 Mon, 14 Jun 2010 14:26:32 +0100 3670144 http://www.medworm.com/index.php?rid=3651372&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F5t73nj21533q0311%2F Abstract  Two genetically different pig breeds, the Korean native pig (KNP) and the Western meat-producing Landrace, show breed-specific traits in stress responsiveness (stress hormone levels), growth performance (live weight), and meat quality (intramuscular fat content). We analyzed expression levels within the proteome and transcriptome of the longissimus muscles of both breeds using two-dimensional electrophoresis (2-DE) and microarray analysis. We constructed a porcine proteome database focused mainly on mitochondrial proteins. In total, 101 proteins were identified, of which approximately 60% were metabolic enzymes and mitochondrial proteins. We screened several proteins and genes related to stress and metabolism in skeletal muscles using comparative analysis. In parti... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=3651372 Tue, 08 Jun 2010 07:05:59 +0100 3651372 http://www.medworm.com/index.php?rid=3643688&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F021317622m42p047%2F Abstract  Congenic strains continue to be a fundamental resource for dissecting the genetic basis of complex traits. Traditionally, genetic variants (QTLs) that account for phenotypic variation in a panel of congenic strains are sought first by comparing phenotypes for each strain to the host (reference) strain, and then by examining the results to identify a common chromosome segment that provides the best match between genotype and phenotype across the panel. However, this “common-segment” method has significant limitations, including the subjective nature of the genetic model and an inability to deal formally with strain phenotypes that do not fit the model. We propose an alternative that we call “sequential” analysis and that is based on a unique principle of QT... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=3643688 Thu, 03 Jun 2010 16:46:24 +0100 3643688 http://www.medworm.com/index.php?rid=3628459&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F45x61mn6k22n7515%2F Abstract  The Tail Suspension Test (TST), which measures behavioral despair, is widely used as an animal model of human depressive disorders and antidepressant efficacy. In order to identify novel genes involved in the regulation of TST performance, we crossed an inbred strain exhibiting low immobility in the TST (RIIIS/J) with two high-immobility strains (C57BL/6J and NZB/BlNJ) to create two distinct F2 hybrid populations. All F2 offspring (n = 655) were genotyped at high density with a panel of SNP markers. Whole-genome interval mapping of the F2 populations identified statistically significant quantitative trait loci (QTLs) on mouse chromosomes (MMU) 4, 6, and X. Microarray analysis of hippocampal gene expression in the three parental strains was used to identif... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=3628459 Fri, 28 May 2010 17:56:07 +0100 3628459 http://www.medworm.com/index.php?rid=3628460&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk650j7u883460428%2F Abstract  Copy-number variation in the human genome can be disease-causing or phenotypically neutral. This type of genetic rearrangement associated with human chromosome 21 (Hsa21) underlies partial Monosomy 21 and Trisomy 21. Mental retardation is a major clinical manifestation of partial Monosomy 21. To model this human chromosomal deletion disorder, we have generated novel mouse mutants carrying heterozygous deletions of the 2.3- and 1.1-Mb segments on mouse chromosome 10 (Mmu10) and Mmu17, respectively, which are orthologous to the regions on human 21q22.3, using Cre/loxP-mediated chromosome engineering. Alterations of the transcriptional levels of genes within the deleted intervals reflect gene-dosage effects in the mutant mice. The analysis of cognitive behaviors shows... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=3628460 Fri, 28 May 2010 17:56:06 +0100 3628460 http://www.medworm.com/index.php?rid=3602378&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fm11656w3j67l8492%2F Content Type Journal ArticleDOI 10.1007/s00335-010-9265-7Authors Amy F. Eisener-Dorman, University of North Carolina Department of Psychiatry, School of Medicine Chapel Hill NC 27599 USAJohn P. Didion, University of North Carolina Department of Genetics, Carolina Center for Genome Sciences and Lineberger Comprehensive Cancer Center Chapel Hill NC 27599 USACristina Santos, University of North Carolina Division of Pharmacotherapy and Experimental Therapeutics, Institute of Pharmacogenomics and Individualized Therapy Chapel Hill NC 27599 USAJohn D. Calaway, University of North Carolina Department of Genetics, Carolina Center for Genome Sciences and Lineberger Comprehensive Cancer Center Chapel Hill NC 27599 USA Journal Mammalian GenomeOnline ISSN 1432-1777Print ISSN 0938-8990 (Sour... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=3602378 Sat, 22 May 2010 16:47:24 +0100 3602378 http://www.medworm.com/index.php?rid=3602379&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj5224548301m5954%2F In this study we investigated the genomic location of CYP1D genes in mammals and other vertebrates in silico. We also performed phylogenetic analysis and calculated the identities and similarities of CYP1D sequences. The data from synteny and phylogenetic analyses of CYP1D genes demonstrated the evolutionary history of the CYP1 gene family. The results suggested that CYP1D became a nonfunctional pseudogene in human and bovine species; however, several other mammals possess functional CYP1D genes. The promoter regions of CYP1D genes were also examined. Unlike other CYP1 isoforms, few xenobiotic responsive element (XRE)-like sequences were found upstream of the CYP1D genes. Analysis of mammalian CYP1Ds also provided new insight into the relationship between CYP1 genes and the aryl hydr... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=3602379 Fri, 21 May 2010 21:01:26 +0100 3602379 http://www.medworm.com/index.php?rid=3572554&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk84136v553l02507%2F Abstract  The use of mouse blood as a model for human blood is often considered in the development of clinically relevant, gene expression-based disease biomarkers. However, the ability to derive biologically meaningful insights from microarray-based gene expression patterns in mouse whole blood, as in human whole blood, is hindered by high levels of globin mRNA. In order to characterize the effects of globin reduction on gene expression of peripheral mouse blood, we performed gene set enrichment analysis on genes identified as expressed in blood via microarray-based genome-wide transcriptome analysis. Depletion of globin mRNA enhanced the quality of microarray data as shown by improved gene expression detection and increased sensitivity. Compared to genes expressed in whol... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=3572554 Sun, 16 May 2010 07:00:46 +0100 3572554 http://www.medworm.com/index.php?rid=3572555&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F255m17n4lq86231k%2F Abstract  Quantitative trait locus (QTL) mapping in the mouse typically utilizes inbred strains that exhibit significant genetic and phenotypic diversity. The development of dense SNP panels in a large number of inbred strains has eliminated the need to maximize genetic diversity in QTL studies as plenty of SNP markers are now available for almost any combination of strains. We conducted a QTL mapping experiment using both a backcross (N2) and an intercross (F2) between two genetically similar inbred mouse strains: C57BL/6J (B6) and C57L/J (C57). A set of additive QTLs for activity behaviors was identified on Chrs 1, 9, 13, and 15. We also identified additive QTLs for anxiety-related behaviors on Chrs 7, 9, and 16. A QTL on Chr 11 is sex-specific, and we revealed pairwise in... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=3572555 Sat, 15 May 2010 08:00:45 +0100 3572555 http://www.medworm.com/index.php?rid=3541349&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fx8q2w4r24w031162%2F We examined mitochondrial genomes of the hypertensive strains: the Dahl Salt-Sensitive (S) rat, the Spontaneously Hypertensive Rat (SHR), and the Albino Surgery (AS) rat, and the relatively normotensive strains: the Dahl Salt-Resistant (R) rat, the Milan Normotensive Strain (MNS), and the Lewis rat (LEW). These strains were used previously for linkage analysis for blood pressure (BP) in our laboratory. The results provide evidence to suggest that variations in the mitochondrial genome do not account for observed differences in blood pressure between the S and R rats. However, variants were detected among the mitochondrial genomes of the various hypertensive strains, S, SHR, and AS, and also among the normotensive strains R, MNS, and LEW. A total of 115, 114, 106, 106, and 16 variati... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=3541349 Wed, 05 May 2010 08:11:23 +0100 3541349 http://www.medworm.com/index.php?rid=3502601&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fw6810340287515kj%2F Abstract  Laboratory Animal Management Assistant (LAMA) is an internet-based system for tracking large laboratory mouse colonies. It has a user-friendly interface with powerful search capabilities that ease day-to-day tasks such as tracking breeding cages and weaning litters. LAMA was originally developed to manage hundreds of new mouse strains generated by a large functional genomics program, the Pleiades Promoter Project (http://www.pleiades.org). The software system has proven to be highly flexible, suitable for diverse management approaches to mouse colonies. It allows custom tagging and grouping of animals, simplifying project-specific handling and access to data. Finally, LAMA was developed in close collaboration with mouse technicians to ease the transition from paper... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=3502601 Thu, 22 Apr 2010 09:20:45 +0100 3502601 http://www.medworm.com/index.php?rid=3470876&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F75227577x307l478%2F Abstract  MTF-1 is a crucial transcription factor involved in the cellular response to heavy-metal load and other stresses by specifically binding to metal response elements (MREs). Thus far only a handful of direct target genes are known for this transcription factor, limiting our understanding of the biological network it governs. In this article we try to employ a computational strategy based on the generation of literature-based positional weight matrices (PWM) and log-likelihood scoring of the candidate binding sites (BSs) for identification of direct targets of the transcription factor MTF-1 in human and mouse. Through comparisons, we explore the conservation and unique characteristics between two species. Our results show that the numbers of MREs differ dramatically ... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=3470876 Sun, 11 Apr 2010 05:49:41 +0100 3470876 http://www.medworm.com/index.php?rid=3393722&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F26v30u3l082p7772%2F Erratum to: A genome-wide scan for quantitative trait loci affecting serum glucose and lipids in a White Duroc × Erhualian intercross F2 population Content Type Journal ArticleCategory ErratumDOI 10.1007/s00335-010-9256-8Authors Rongrong Chen, Jiangxi Agricultural University Key Laboratory for Animal Biotechnology of Jiangxi Province and the Ministry of Agriculture of China Nanchang 330045 ChinaJun Ren, Jiangxi Agricultural University Key Laboratory for Animal Biotechnology of Jiangxi Province and the Ministry of Agriculture of China Nanchang 330045 ChinaWanbo Li, Jiangxi Agricultural University Key Laboratory for Animal Biotechnology of Jiangxi Province and the Ministry of Agriculture of China Nanchang 330045 ChinaXiang Huang, Jiangxi Agricultural University Key Laboratory for Anima... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=3393722 Sat, 20 Mar 2010 11:03:44 +0100 3393722 http://www.medworm.com/index.php?rid=3357674&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fd7u7338201035ll3%2F We describe the systematic application of complementary computational and experimental techniques to detect and document functional genetic variation in a trait-associated regulatory region. The results provide insight into cis and trans transcriptional mechanisms whereby common variation at PNMT can give rise to quantitative changes in human physiological and disease traits. Thus, PNMT variants in cis may interact with nuclear factors in trans to govern adrenergic activity. Content Type Journal ArticleDOI 10.1007/s00335-010-9253-yAuthors Juan L. Rodríguez-Flores, University of California at San Diego School of Medicine Department of Medicine, Institute for Genomic Medicine La Jolla CA USAKuixing Zhang, University of California at San Diego School of Medicine Department of Medici... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=3357674 Wed, 10 Mar 2010 15:36:02 +0100 3357674 http://www.medworm.com/index.php?rid=3357675&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fl354544n59757725%2F Abstract  We previously identified a Chr 15 quantitative trait locus (QTL) Fob3b in lines of mice selected for high (Fat line) and low (Lean line) body fat content that represent a unique model of polygenic obesity. Here we genetically dissected the Fob3b interval by analyzing the phenotypes of eight overlapping congenic lines and four F2 congenic intercrosses and prioritized candidates by bioinformatics approaches. Analyses revealed that the Fob3b QTL consists of at least two separate linked QTLs Fob3b1 and Fob3b2. They exhibit additive inheritance and are linked in coupling with alleles originating from the Lean line, decreasing obesity-related traits. In further analyses, we focused on Fob3b1 because it had a larger effect on obesity-related traits than Fob3b2, e.g., the dif... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=3357675 Wed, 10 Mar 2010 15:36:01 +0100 3357675 http://www.medworm.com/index.php?rid=3330338&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F6089363858558343%2F Abstract  Mutations in the human OCRL gene, which encodes a phosphatidylinositol(4,5)bisphosphate 5-phosphatase, result in the X-linked oculocerebrorenal syndrome of Lowe. Mice with a targeted disruption of Ocrl have no phenotypic abnormalities. Targeted disruption of its closest paralog, Inpp5b, causes male infertility in the 129S6 background. Mice with disruptions of both genes are lost in utero prior to 9.5-10.5 dpc, indicating that there is a functional overlap between the two paralogs early in development. We analyzed the pattern of X-inactivation in four tissues of distinct embryonic origin from Ocrl wt/−;Inpp5b −/− females to explore the timing and tissue distribution of the functional overlap. X-inactivation was strongly skewed against the disrupted Ocrl �... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=3330338 Tue, 02 Mar 2010 10:00:26 +0100 3330338 http://www.medworm.com/index.php?rid=3313916&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fp238522r26456566%2F In this study, to elucidate the genetic background of development of ovarian cysts, we performed quantitative trait locus (QTL) analysis using 120 microsatellite markers, which cover the whole genome of murine chromosomes, and 213 backcross progenies between female MRL and male C57BL/6N mice. The quantitative trait measured was the circumferences of rete ovarii or ovarian cysts. As a result, suggestive linkages were detected on Chrs 3, 4, 6, and 11, but significant linkages were located on Chr 14 by interval mapping. We thereby designated the 27.5-cM region of Chr 14 “MRL Rete Ovarian Cysts (mroc).” The peak regions of Chrs 4 and 14 in particular showed a close additive interaction (p < 0.00001). From these results we concluded that multiple loci on Chrs 3, 4, 6, 11, ... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=3313916 Thu, 25 Feb 2010 06:50:55 +0100 3313916 http://www.medworm.com/index.php?rid=3278883&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fy51m40j115823246%2F In conclusion, testis weight is reduced in MRL mice due to apoptosis of germ cells caused by mutations in loci on Chrs 1 and 2. Content Type Journal ArticleDOI 10.1007/s00335-010-9251-0Authors Saori Otsuka, Hokkaido University Office for Faculty Development and Teaching Enriched Veterinary Medicine, Graduate School of Veterinary Medicine Sapporo 060-0818 JapanYuka Namiki, Harvard Medical School Department of Molecular Biology, Massachusetts General Hospital Boston MA 02114 USAOsamu Ichii, Hokkaido University Laboratory of Anatomy, Graduate School of Veterinary Medicine Kita 18 Nishi 9, Kita-ku Sapporo 060-0818 JapanYoshiharu Hashimoto, Hokkaido University Office for Faculty Development and Teaching Enriched Veterinary Medicine, Graduate School of Veterinary Medicine Sapporo 060-081... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=3278883 Mon, 15 Feb 2010 17:59:01 +0100 3278883 http://www.medworm.com/index.php?rid=3257756&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Flj6462u3138801w0%2F Abstract  The Jackson Laboratory Colony Management System (JCMS) is a software application for managing data and information related to research mouse colonies, associated biospecimens, and experimental protocols. JCMS runs directly on computers that run one of the PC Windows® operating systems, but can be accessed via web browser interfaces from any computer running a Windows, Macintosh®, or Linux® operating system. JCMS can be configured for a single user or multiple users in small- to medium-size work groups. The target audience for JCMS includes laboratory technicians, animal colony managers, and principal investigators. The application provides operational support for colony management and experimental workflows, sample and data tracking through transaction-based data... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=3257756 Sat, 06 Feb 2010 17:59:23 +0100 3257756 http://www.medworm.com/index.php?rid=3248401&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fu01w57574uv3455u%2F Abstract  The remarkable success in mapping genes linked to a number of disease traits using genome-wide association studies (GWAS) in human cohorts has renewed interest in applying this same technique in model organisms such as inbred laboratory mice. Unlike humans, however, the limited genetic diversity in the ancestry of laboratory mice combined with selection pressure over the past decades have yielded an intricate population genetic structure that can complicate the results obtained from association studies. This problem is further exacerbated by the small number of strains typically used in such studies where multiple spurious associations arise as a result of random chance. We sought to empirically assess the viability of GWAS in inbred mice using hundreds of express... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=3248401 Thu, 04 Feb 2010 18:09:40 +0100 3248401 http://www.medworm.com/index.php?rid=3242717&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F5q52061nw7002xlv%2F Abstract  Discovery of genes that confer resistance to diseases such as diet-induced obesity could have tremendous therapeutic impact. We previously demonstrated that the C57BL/6J-ChrA/J/NaJ panel of chromosome substitution strains (CSSs) is a unique model for studying resistance to diet-induced obesity. In the present study, three replicate CSS surveys showed remarkable consistency, with 13 A/J-derived chromosomes reproducibly conferring resistance to high-fat-diet-induced obesity. Twenty CSS intercrosses, one derived from each of the 19 autosomes and chromosome X, were used to determine the number and location of quantitative trait loci (QTLs) on individual chromosomes and localized six QTLs. However, analyses of mean body weight in intercross progeny versus C57BL/6J provi... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=3242717 Wed, 03 Feb 2010 06:48:16 +0100 3242717 http://www.medworm.com/index.php?rid=3224649&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fc356838203374368%2F Abstract  Members of the CHD protein family play key roles in gene regulation through ATP-dependent chromatin remodeling. This is facilitated by chromodomains that bind histone tails, and by the SWI2/SNF2-like ATPase/helicase domain that remodels chromatin by moving histones. Chd6 is ubiquitously expressed in both mouse and human, with the highest levels of expression in the brain. The Chd6 gene contains 37 exons, of which exons 12-19 encode the highly conserved ATPase domain. To determine the biological role of Chd6, we generated mouse lines with a deletion of exon 12. Chd6 without exon 12 is expressed at normal levels in mice, and Chd6 Exon 12 −/− mice are viable, fertile, and exhibit no obvious morphological or pathological phenotype. Chd6 Exon 12 −/− mice lack coor... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=3224649 Thu, 28 Jan 2010 17:59:40 +0100 3224649 http://www.medworm.com/index.php?rid=3141504&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fn2628m478n07334m%2F Abstract  Mammalian epidermis is a stratified epithelium that serves as a barrier protecting the organism from mechanical stress and dehydration. Previous studies have demonstrated the importance of the actin cytoskeleton in the establishment of a functional skin epithelium. Despite what is known about the actin cytoskeleton in epithelial sheet formation, the molecules important for controlling the actin cytoskeleton during epidermal development have not been determined. Serum response factor (SRF) is a transcription factor that is considered to be an important regulator of the actin cytoskeleton. To examine the role of SRF in the developing mouse epidermis, we have employed gene targeting to ablate Srf in keratinocytes. Conditional inactivation of Srf during the embryonic t... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=3141504 Sat, 02 Jan 2010 16:57:57 +0100 3141504 http://www.medworm.com/index.php?rid=3132858&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fa582q32l66l2u277%2F Abstract  Chronic pastern dermatitis (CPD), also known as chronic progressive lymphedema (CPL), is a skin disease that affects draft horses. This disease causes painful lower-leg swelling, nodule formation, and skin ulceration, interfering with movement. The aim of this whole-genome scan was to identify quantitative trait loci (QTL) for CPD in German draft horses. We recorded clinical data for CPD in 917 German draft horses and collected blood samples from these horses. Of these 917 horses, 31 paternal half-sib families comprising 378 horses from the breeds Rhenish German, Schleswig, Saxon-Thuringian, and South German were chosen for genotyping. Each half-sib family was constituted by only one draft horse breed. Genotyping was done for 318 polymorphic microsatellites evenly... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=3132858 Tue, 29 Dec 2009 06:53:38 +0100 3132858 http://www.medworm.com/index.php?rid=3123234&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fh7274t314l283658%2F Abstract  C57BL/6 J (B6) and CAST/EiJ (CAST), the inbred strain derived from M. musculus castaneus, differ in nutrient intake behaviors, including dietary fat and carbohydrate consumption in a two-diet-choice paradigm. Significant quantitative trait loci (QTLs) for carbohydrate (Mnic1) and total energy intake (Kcal2) are present between these strains on chromosome (Chr) 17. Here we report the refinement of the Chr 17 QTL in a subcongenic strain of the B6.CAST- D17Mit19-D17Mit91 congenic mice described previously. This new subcongenic strain possesses CAST Chr 17 donor alleles from 4.8 to 45.4 Mb on a B6 background. Similar to CAST, the subcongenic mice exhibit increased carbohydrate and total calorie intake per body weight, while fat intake remains equivalent. Un... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=3123234 Thu, 24 Dec 2009 19:56:21 +0100 3123234 http://www.medworm.com/index.php?rid=3121849&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fw11x30486n8r1206%2F Abstract  Multiple Genome Rearrangement (MGR) analysis was used to define the trajectory and pattern of chromosome rearrangement within muroid rodents. MGR was applied using 107 chromosome homologies between Mus, Rattus, Peromyscus, the muroid sister taxon Cricetulus griseus, and Sciurus carolinensis as a non-Muroidea outgroup, with specific attention paid to breakpoint reuse and centromere evolution. This analysis revealed a high level of chromosome breakpoint conservation between Rattus and Peromyscus and indicated that the chromosomes of Mus are highly derived. This analysis identified several conserved evolutionary breakpoints that have been reused multiple times during karyotypic evolution in rodents. Our data demonstrate a high level of reuse of breakpoints among muroid ... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=3121849 Wed, 23 Dec 2009 22:19:07 +0100 3121849 http://www.medworm.com/index.php?rid=3121850&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fdl0358464451g4u8%2F Abstract  A new spontaneous mouse mutant was characterized by closed eyelids at weaning and without apparent eyes (provisional gene name, eyeless; provisional gene symbol, eyl). The mutation follows a recessive pattern of inheritance and was mapped to the region of chromosome 19 containing Pitx3. Genetic complementation tests using Pitx3 ak/+ mice confirmed eyl as a new allele of Pitx3 (Pitx3 eyl ). Sequencing of the Pitx3 gene in eyl mutants identified an inserted G after cDNA position 416 (416insG; exon 4). The shifted open reading frame is predicted to result in a hybrid protein still containing the Pitx3 homeobox, but followed by 121 new amino acids. The novel Pitx3 eyl/eyl mutants expressed ophthalmological and brain defects similar to Pitx3 ak/ak mice: mic... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=3121850 Wed, 23 Dec 2009 22:19:02 +0100 3121850 http://www.medworm.com/index.php?rid=3117994&cid=s_33324_50_f&fid=33324&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F623m0466105605u0%2F Abstract  Excessive alcohol (ethanol) consumption is the hallmark of alcohol use disorders. The F1 hybrid cross between the C57BL/6J (B6) and FVB/NJ (FVB) inbred mouse strains consumes more ethanol than either progenitor strain. The purpose of this study was to utilize ethanol-drinking data and genetic information to map genes that result in overdominant (or heterotic) ethanol drinking. About 600 B6 × FVB F2 mice, half of each sex, were tested for ethanol intake and preference in a 24-h, two-bottle water versus ethanol choice procedure, with ascending ethanol concentrations. They were then tested for ethanol intake in a Drinking in the Dark (DID) procedure, first when there was no water choice and then when ethanol was offered versus water. DNA samples were obtained and ge... Mammalian Genome journals http://www.medworm.com/rss/comments.php?id=3117994 Mon, 21 Dec 2009 22:59:46 +0100 3117994