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  • 17th International Mouse Genome Conference (2003)
    3 Conti D 1 Witte J 2 Lander E 1 Nadeau J Institutions 1 Case Western Reserve University 2 Whitehead Institute Massachusetts Institute of Technology 3 University of Southern California The new panel of B6 A chromosome substitution strains provides a powerful tool for dissecting complex genetic traits Because the C57BL 6J and A J inbred strains differ in their susceptibility to obesity on a high fat high sucrose diet we used the B6 A panel to identify the chromosomal location of genes associated with resistance to diet induced obesity We placed 20 males from each strain on a high fat high sucrose diet at 35 days of age and collected body weights every two weeks for approximately 100 days We found that A J derived chromosomes 3 4 6 7 8 10 11 12 13 14 15 16 17 18 and Y conferred resistance to diet induced obesity whereas chromosomes 1 2 9 19 and X did not confer resistance Preliminary studies of F2 intercross progeny derived from B6 A1 B6 A2 B6 A9 B6 A19 and B6 AX suggest that these chromosomes harbor QTLs that have opposing effects on obesity resistance Overall by analyzing a total of 400

    Original URL path: http://www.imgs.org/Archive/abstracts/2003abstracts/file211.shtml (2016-02-17)
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  • 17th International Mouse Genome Conference (2003)
    Loredo Osti J C 1 2 Morgan K 1 2 3 Malo D Institutions 1 Department of Human Genetics 2 Center for the Study of Host Resistance 3 Department of Medicine McGill University The Gram negative bacteria Salmonella cause a broad spectrum of clinical diseases in humans We have developed a model to study the contribution of genes to the susceptibility of 129sv and C57BL 6J mice to Salmonella enteritidis during the late phase of infection A genome scan performed on 302 C57BL 6J x 129sv F2 progeny identified two highly significant linkages on chromosomes 1 Ses1 and 7 Ses2 with respective LOD scores of 9 9 p 1 4x10 11 at D1Mcg5 and 4 0 p 1 9x10 5 at D7Mit62 and one highly suggestive QTL on chromosomes 15 Ses3 with a LOD score 3 4 p 1 2x10 4 All QTLs were associated with disease susceptibility in 129sv mice and their estimated effects on the bacterial clearance were greater in females Using a model of three loci with interaction between Ses1 and Ses2 and sex as a covariate the three QTLs explained 32 of the phenotypic variance The candidacy of Slc11a1 as the gene for Ses1 was evaluated

    Original URL path: http://www.imgs.org/Archive/abstracts/2003abstracts/file212.shtml (2016-02-17)
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  • 17th International Mouse Genome Conference (2003)
    INTERACTING QTL ON CHROMOSOMES 6 AND 15 UNDERLIE SALT INDUCED HYPERTENSION BY REDUCING SODIUM EXCRETION DiPetrillo K The Jackson Laboratory Co Authors Sheehan S Whitmore H Taylor E and Paigen B Institutions The Jackson Laboratory Hypertension represents a significant medical problem in Western societies Salt sensitive hypertension confers increased risk of cardiovascular and renal disease and salt sensitive changes in blood pressure are associated with increased mortality We previously identified interacting quantitative trait loci QTL C57BL 6J Chr 15 with A J Chr 6 in mice that contribute to salt sensitive hypertension In the present study we determined that mice containing high blood pressure alleles at both interacting loci B6 A Chr 6 consomic display significantly reduced urinary sodium concentrations compared to C57BL 6J mice 189 9 19 vs 285 0 7 mM on 1 salt water Using a series of reciprocal overlapping congenic strains we subsequently narrowed the Chr 6 QTL region to 27cM In addition data from the overlapping congenic strains suggests the presence of two genes underlying the QTL Plausible candidate genes within this region include Scnn1a epithelial sodium channel alpha subunit and Tnfrsf1a tumor necrosis factor receptor 1 In conclusion decreased renal sodium excretion is likely

    Original URL path: http://www.imgs.org/Archive/abstracts/2003abstracts/file213.shtml (2016-02-17)
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  • 17th International Mouse Genome Conference (2003)
    H Co Authors Kim K Bell T Ideraabdullah F Pardo Manuel de Villena F Institutions In mammals meiotic drive is achieved by preferential segregation of one chromosome over another to the functional product of female meiosis Although meiotic drive is a well known exception to Mendel s law of segregation the molecular mechanisms are not understood Two components are required in all meiotic drive systems the Responder and the Distorter The Distorter is the effector in the system and drives alleles at the Responder The goal of this project is molecular identification of the Distorter in the Om Ovum mutant meiotic drive system Using recombination mapping we have defined a 300kb candidate interval for the Distorter locus on mouse chromosome 11 This locus was named Shade for S perm ha ploid d istorter e lement We have compiled the phenotypes and haplotypes for this region in four classical strains C57BL 6J A J DBA2 J and 129X1 SvJ Within the candidate interval there is a 200kb region containing four genes where there is complete haplotype phenotype concordance Interestingly within the region of concordance there are two missense mutations and three UTR mutations We also characterized the drive phenotype for 11

    Original URL path: http://www.imgs.org/Archive/abstracts/2003abstracts/file214.shtml (2016-02-17)
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  • 17th International Mouse Genome Conference (2003)
    Table of Contents Sponsor Exhibitor List Awards Photographs POSTER 167 GENETIC AND ENVIRONMENTAL INTERACTIONS IN A MURINE OBESITY MODEL Ehrich T Washington University Co Authors Kenney J Hrbek T Wang B Pletscher L Cheverud J Institutions Washington University Despite billions of dollars spent every year on weight loss as well as the continuing public health campaign being waged by physicians and governmental agencies the prevalence of obesity in the United States and worldwide continues to rise Most experts agree that the modern obesity pandemic is an environmental condition of a post industrial society acting on a human genome that evolved under the threat of famine While there has been some progress in finding human genes that respond to a modern environment in generating the obese phenotype complications with human population mapping remain considerable Mouse models derived from inbred lines allow rigorous genetic analysis under carefully controlled environmental conditions in a mammalian system We examine an array of obesity and diabetes related phenotypes in an F16 advanced intercross line AIL derived from SM J and LG J strain mice that has been fed a high fat 43 energy from fat or low fat 15 energy from fat diet A quantitative genetic

    Original URL path: http://www.imgs.org/Archive/abstracts/2003abstracts/file215.shtml (2016-02-17)
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  • 17th International Mouse Genome Conference (2003)
    Imaging The Genetics and Genomics of Infectious Disease Verne Chapman Memorial Lecture Table of Contents Sponsor Exhibitor List Awards Photographs POSTER 168 A SYNTHETIC MUTANT ON CHR 17 IS STERILE DUE TO LACK OF SPERM FLAGELLAE Elliot R Roswell Park Cancer Inst Co Authors Tabaczynski D Pazik J Hohman C Institutions Roswell Park Cancer Inst Male F1 hybrids between inbred strains and M macedonicus are sterile To determine the genetic basis for this sterility C57BL 6J x M macedonicus F1 females were mated to C57BL 10J A genome wide scan with 92 SSLPs was performed for 141 male progeny of this cross and QTLs accounting for about 50 of the testis weight variance were identified on proximal Chrs 17 and X To confirm these findings a congenic line C57BL 6 MAC 17 has been constructed The congenic interval extends from position 0 to position 23 on Chr 17 Congenic males have testes weighing about 0 15 gm compared to weights of about 0 2 gm for the parents Testis histology shows a lack of sperm tails Tubules become plugged with sperm heads that are not released from Sertoli cells Subcongenic males derived during the breeding have been homozygosed Overlapping homozygous

    Original URL path: http://www.imgs.org/Archive/abstracts/2003abstracts/file216.shtml (2016-02-17)
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  • 17th International Mouse Genome Conference (2003)
    Amsterdam the Netherlands Co Authors 1 Vos M 2 Demant P 1 Kraal G Institutions 1 VU University Medical Center Amsterdam the Netherlands 2 Roswell Park Cancer Institute Buffalo USA Susceptibility to common diseases like cancer atherosclerosis infectious diseases and autoimmune diseases is influenced by multiple genetic factors On the one hand each of these diseases has its own distinct etiology and is therefore influenced by disease specific susceptibility genes On the other hand some susceptibility genes may affect multiple diseases by functioning systemically Our goal is to identify systemically acting susceptibility genes by studying the genetics of macrophage characteristics because of the strong implications of macrophages in initiation and progression of various diseases Bone marrow derived macrophages BMMf were obtained from individual mice of F2 crosses produced between several OcB 9 Dem derived inbred strains and their common background strain O20 A resulting in segregation of about 10 of the genome that is known to contain 11 out of 30 previously mapped susceptibility to lung cancer Sluc loci BMMf were subjected to a series of assays including stimulation with lipopolysaccharides upon which secretion of TNFα and IL 12p40 was measured by ELISA and expression of inducible nitric oxide synthase

    Original URL path: http://www.imgs.org/Archive/abstracts/2003abstracts/file217.shtml (2016-02-17)
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  • 17th International Mouse Genome Conference (2003)
    G A 1 Nijkamp F P 2 Demant P 1 Van Oosterhouta A J M Institutions 1 Utrecht University 2 RPCI Buffalo Allergic asthma is a heterogeneous and genetically complex disease characterized by allergen specific IgE eosinophilic airway inflammation and hyperresponsiveness to bronchospasmogenic stimuli We have used the Recombinant Congenic Strains of mice to facilitate the mapping of genes controlling these asthma traits We compared 19 CcS Dem strains which each carry a random set of 12 5 of genes from the Th1 responder strain STS and 87 5 from the Th2 responder strain BALB c Mice were sensitized with ovalbumin OVA and repeatedly challenged by inhalation of OVA aerosol Before and after OVA challenges serum was obtained and airway responsiveness to nebulized methacholine 1 5 50 mg ml determined Bronchoalveolar lavage BAL was performed and number of leukocytes and Th2 cytokinelevels were determined Although serum levels of OVA specific IgE after challenge differ strongly between strains only the parental strain STS did not show elevated IgE levels CcS Dem strains 5 11 12 15 and 16 do not display significant airway hyperresponsiveness after OVA inhalation compared to responsiveness before challenge In addition CcS Dem 5 has the lowest serum

    Original URL path: http://www.imgs.org/Archive/abstracts/2003abstracts/file218.shtml (2016-02-17)
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