METABOLIC AND GENETIC MARKERS FOR DIETARY OBESITY

描述：遗传因素在确定以下风险方面很重要： 肥胖的发展是环境因素，如百分比 饮食中的脂肪。 长期目标是描述基因的特征， 当受到高脂肪饮食的挑战时， 饮食. 韦斯特博士使用了两种菌株的杂交，一种对 膳食脂肪诱导肥胖和一个抵抗，并确定了六个位点， 对膳食脂肪的敏感性有显著影响。 的 最初的目的是1）完成控制基因座的连锁图， AKR/J x SWR/J小鼠对饮食性肥胖的不同敏感性 模型; 2）评估与饮食相关的特定遗传位点的作用 AKR/J x SWR/J模型中的肥胖症在其他几种遗传模型中， 饮食性肥胖; 3）为四个基因座开发同类菌株;以及 4)以评估这些位点上特定候选基因的作用。 的 申请人取得了很好的进展，完成了基因分型， 初交鉴定6-7个位点，构建了多个 与N5代同源，并测试几个候选基因。 的 目前的建议是确定两个基因座的基因。 第一 具体目标是使用精细映射和特征化的策略 在一个小的染色体区域表达序列，以确定 小鼠近端15号染色体上的基因对 身体脂肪 第12染色体QTL中的候选基因是Mod 1 r， 转录因子，其影响结构基因的转录， 参与碳水化合物和脂肪代谢的苹果酸酶。 具体目标2 将确定AKR/J和SWR/J小鼠在Mod 1 r上是否携带不同的等位基因 调节位点和精细定位Mod 1 r位点。

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.