The Role of Candidate Genes in Lipoprotein Metabolism and Atherosclerosis Susceptibility. Creation and Study of Transgenic and Knockout Mouse Models. The Role of Candidate Genes in Lipoprotein Metabolism and Atherosclerosis Susceptibility. Creation and Study of Transgenic and Knockout Mouse Models. Lipoprotein levels are major risk factors for atherosclerotic cardiovascular disease.
Lipoproteins are macromolecular complexes of lipids and proteins, called apolipoproteins.
Apolipoproteins coat lipoprotein particles not only serving as structural constituents, but also regulating lipoprotein synthesis and secretion, and acting as cofactors for lipoprotein interconversion reactions that occur in plasma and as ligands for lipoprotein receptors which regulate lipoprotein removal and destruction. E. Our laboratory played a seminal role in the isolation of the genes coding for these proteins and identified genetic variants involved in lipoprotein disorders. The most prominent of these was identification of the 3 common forms of apo E, E4, E3 and E2. This genetic variation influences plasma LDL cholesterol levels and coronary heart disease susceptibility, and was recently shown to have a major influence on susceptibility to Alzheimer's disease. To better understand the roles of the individual apolipoproteins in lipoprotein metabolism we have made transgenic and knockout mice for almost all of them.