METABOLIC AND GENETIC MARKERS FOR DIETARY OBESITY

描述：遗传因素在决定癌症风险方面很重要。 肥胖的发展以及环境因素，如百分比 饮食中的脂肪含量。长期目标是描述基因的特征 当面对高脂肪挑战时肥胖的易感性的基础 节食。韦斯特博士使用了两个菌株之间的杂交，其中一个菌株对 膳食脂肪诱导肥胖和1个抗性，并确定了6个基因座 对饮食脂肪的易感性有显著影响。这个 最初的目标是1)完成一张控制基因座的连锁图谱 AKR/J×SWR/J小鼠对饮食肥胖的不同敏感性 模型；2)评估与饮食相关的特定遗传基因座的作用 AKR/J x SWR/J模型中肥胖在其他几个遗传模型中的研究 饮食肥胖；3)为其中四个基因座培育同源菌株；以及 4)评估特定候选基因在这些基因座上的作用。这个 申请人取得了很好的进展，完成了对 与鉴定出的6-7个座位的初交，构建了多个 N5代的同源基因，并测试了几个候选基因。这个 目前的建议是确定其中两个基因座的基因。第一 具体目的是使用精细映射的策略和刻画 在一个小的染色体区域中的表达序列，以便识别 小鼠近端15号染色体上的基因对 身体脂肪。12号染色体QTL中的一个候选基因是mod1r，a 影响结构基因转录的转录因子 苹果酸酶参与碳水化合物和脂肪代谢。具体目标2 将确定AKR/J和SWR/J小鼠在MOD1r是否携带不同的等位基因 并精细定位了mod1r基因座。

DESCRIPTION: Genetic factors are important in determining the risk for development of obesity as are environmental factors such as the percentage of fat in the diet. The long range goal is to characterize the genetic basis for the predisposition to obesity when challenged with a high-fat diet. Dr. West used an intercross between two strains, one susceptible to dietary fat induced obesity and one resistant, and identified six loci which have a significant effect on the susceptibility to dietary fat. The original Aims were to 1) complete a linkage map of the loci controlling differential sensitivity to dietary obesity in the AKR/J x SWR/J mouse model; 2) to evaluate the role of specific genetic loci linked to dietary obesity in the AKR/J x SWR/J model in several other genetic models of dietary obesity; 3) to develop congenic strains for four of the locus; and 4) to evaluate the role of specific candidate genes at these loci. The applicant has made excellent progress, completing the genotyping on the primary cross with the identification of 6-7 loci, constructing a number of congenics to the N5 generation, and testing several candidate genes. The current proposal is identify the gene underlying two of the loci. The first Specific Aim is to use the strategy of fine mapping and the characterization of expressed sequences in a small chromosomal region in order to identify the gene on proximal chromosome 15 of the mouse having a major effect on body fat. A candidate gene in the chromosome 12 QTL is Mod1r, a transcription factor which affects transcription of the structural gene for malic enzyme involved in carbohydrate and fat metabolism. Specific Aim 2 will determine if AKR/J and SWR/J mice carry different alleles at the Mod1r regulatory locus and to fine map the Mod1r locus.