MOLECULAR GENETIC APPROACHES IN ATHEROSCLEROSIS RESEARCH

该项目包括多种分子遗传学方法来研究 正常脂质中的脂蛋白、载脂蛋白和酶 动脉粥样硬化动物模型中的脂质转运和脂质转运。 这些 分子遗传学方法包括：（1）克隆几种 载脂蛋白和脂蛋白脂酶的研究，（2）脂蛋白和 来自应答者和非应答者的重组近交系的载脂蛋白 小鼠，（3）利用种间体细胞杂交和遗传 连锁分析的染色体定位的基因编码的 血清载脂蛋白，和（4）单克隆抗体的使用， 鉴定人载脂蛋白B中的等位基因变体。 中 问题是：载脂蛋白B的等位基因变异如何影响 富含甘油三酯的脂蛋白和LDL的结构和代谢 编码载脂蛋白B的基因是如何表达的，也就是说，哪些因素 控制消息的产生，产生什么消息， 信息处理，以及转录后修饰发生在 载脂蛋白B在富含磷脂酰肌醇的脂蛋白分泌之前 哪些结构性 差异区分各种组织脂蛋白脂肪酶， 因子调控其表达？ 不同的等位基因混合物 其编码不同的载脂蛋白在运输中的功能， 应答动物和非应答动物的饮食脂质代谢？ 对 哪条染色体是不同载脂蛋白的基因， 小鼠、大鼠和人类，这些染色体位置是否可以精确定位， 与其他已知基因座的联系

This project includes a variety of molecular genetic approaches to study the lipoproteins, apolipoproteins and enzymes involved in normal lipid transport and lipid transport in animal models for atherosclerosis. These molecular genetic approaches include: (1) The cloning of cDNA for several apolipoproteins and lipoprotein lipase, (2) A study of lipoproteins and apolipoproteins from recombinant inbred lines of responder and nonresponder mice, (3) The use of interspecies somatic cell hybridization and genetic linkage analysis for chromosomal localization of the genes coding for the serum apolipoproteins, and (4) The use of monoclonal antibodies for the identification of allelic variants among the human apo B. Among the questions being asked are: How does allelic variation for apo B affect the structure and metabolism of the triglyceride-rich lipo-proteins and LDL How are the genes which code for apo B expressed, that is, what factors control the production of message, what messages are produced, how is the message processed, and what post transcriptional modifications occur to the apo B before triglyceride-rich lipoproteins are secreted? What structural differences distinguish the various tissue lipoprotein lipases, and what factors regulate their expression? How do various mixtures of the alleles which code for the different apolipoproteins function in the transport and metabolism of dietary lipids in responder and nonresponder animals? On which chromosomes are the genes for the various apolipoproteins located in mouse, rat and man, and can these chromosomal locations be pinpointed and linked to other known loci?