MOLECULAR GENETIC APPROACHES IN ATHEROSCLEROSIS

动脉粥样硬化研究中的分子遗传学方法是 我们的计划项目，重点是表达基因参与 脂质转运和疾病，包括载脂蛋白B基因， LPL和HL，apo AIV，cld和fld相关基因 近交系小鼠的缺陷，以及许多其他缺陷。 五项工程五个核心 密切合作;研究包括最新的技术，以“敲- 基因，微卫星来开发小鼠和人类的连锁图谱 用于数量性状基因座分析，三维结晶 结构分析，并转染原代肝细胞以测试 脂蛋白组装的两步模型。 项目I，ApoB：遗传 多态性和在VLDL生物合成中的作用，探针脂蛋白组装 在分子水平上，研究了两种不同的 单个个体血清中的LDL;项目II，脂肪酶结构- 功能，重点是嵌合LPL和HL，脂肪酶突变和 结晶，项目III，脂蛋白的基因决定簇 表达：小鼠模型，参与apo A-II基因的“敲除” 和载脂蛋白A-IV，以及近交系小鼠的数量性状基因座研究; IV，CAD的遗传因素及其风险，收集 使用人类连锁图谱的CAD多重发病家族 为这些家庭构建，以识别和表征基因 参与动脉粥样硬化。 项目V，脂肪酶的分子遗传学 表达，集中在基因缺陷影响脂肪酶的表达， CLD和FLD小鼠。 支持核心包括核心A、脂蛋白和 用机器人辅助测定法进行脂质分析;核心B，数量性状 基因座和遗传标记;核心C，大规模表达;和核心D， 淋巴母细胞样细胞系。 人类和老鼠遗传学的学科， 分子生物学、生物化学、生物物理学和医学 在这些研究中。

Molecular genetic approaches in atherosclerosis research is the theme of our Program Project which focuses on expression of genes involved in lipid transport and disease, including genes for apo B, for the lipases LPL and HL, for apo AIV, for the genes involved in the cld and fld defects in inbred mice, and many others. Five projects and five cores collaborate closely; research includes the latest techniques to "knock- out" genes, microsatellites to develop both mouse and human linkage maps for quantitative trait loci analysis, crystallization for 3 dimensional structure analysis, and transfection of primary hepatocytes to test the two-step model of lipoprotein assembly. Project I, ApoB: Genetic Polymorphism and Role in VLDL Biosynthesis, probes lipoprotein assembly at eh molecular level, and studies altered levels of the two different LDL in the serum of single individuals; Project II, Lipase Structure- Function, focuses on chimeric LPL and HL, lipase mutations and crystallization, Project III, Gene Determinants of Lipoprotein Expression: Mouse Model, is engaged in "knocking out" genes for apo A-II and apo A-IV, and quantitative trait loci studies in inbred mice; Project IV, Genetic Factors Contributing to CAD and their Risks, collects families with multiple incidence of CAD and uses human linkage maps constructed for these families to identify and characterize genes involved in atherosclerosis. Project V, Molecular Genetics of Lipase Expression, is focused on gene defects affecting lipase expression in the cld and fld mice. The supporting cores include Core A, lipoprotein and lipid analysis with robot assisted assays; Core B, quantitative trait loci and genetic markers; Core C, large scale expression; and Core D, lymphoblastoid cell lines. The disciplines of human and mouse genetics, molecular biology, biochemistry, biophysics and medicine are represented in these studies.