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?
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