The Breslow laboratory has pioneered the study of genetic factors that contribute to atherosclerosis susceptibility. The laboratory isolated and characterized most of the human and mouse apolipoprotein cDNAs and genes and identified apolipoprotein gene variants associated with susceptibility to coronary heart disease, including the 3 common forms of apoE (E4, E3, and E2) and apoA-I variants affecting HDL cholesterol levels. The laboratory also made many of the first induced mutant mouse models in atherosclerosis research, including transgenics that showed the importance of apoA-I production in protection from atherosclerosis and the causative role of apoCIII over production in hypertriglyceridemia. Moreover, in a very early application of the knockout technique, apoE deficient mice were created. These mice develop human-like atherosclerotic lesions, and became the first good small animal model of atherosclerosis. ApoE knockout mice led the way for the mouse to become the major experimental model in atherosclerosis research. Dr. Breslow's laboratory now emphasizes whole genome approaches to understanding the complex genetic basis of atherosclerosis susceptibility and engages in 3 main projects.