Use Of Animal Models To Study Genes That Modulate Atherosclerosis

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In the past year, we have continued to use both commercially available and unique mouse strains that we have developed to investigate the association between lipoprotein metabolism and atherosclerosis. Many of our published papers involving animal models are listed under our other projects. One of our main accomplishments in the past year that is listed under this project is the discovery of a novel gene called DENND5B that we have found to be involved in intestinal chylomicron secretion. The target gene was identified by a phage display library and a complete KO mouse was made confirming the importance of this gene in lipid metabolism. DENNDD5B encodes for a RAB-GTPase like protein that appears to be involved in trafficking of chylomicrons from the Golgi to the plasma membrane, which was uncovered using the KO mouse strain that we made. The other main accomplishment in the past year was the use of our various animal models related to HDL that were used to develop a cell-free assay system to examine the ability of HDL to efflux excess cellular cholesterol. A patent was filed on the assay and we plan to explore in the future its clinical utility as a cardiovascular risk biomarker in human samples. We have also successfully made in the past year but have not published yet a conditional apoC-III KO mice to selectively delete the apoC-III gene in various tissues to examine its effect on triglyceride metabolism.