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Problem Addressed

Good preclinical mouse models of atherosclerotic CHD are essential to understand the pathophysiology of the disease as well as test efficacy of therapeutic options. Currently, the mouse models of atherosclerotic CHD combine co-mutations in SR-BI, apoE, LDLR, or, in some cases PDZK1, with administration of either normal chow or atherogenic diet. These mouse models exhibit occlusive coronary artery disease, myocardial infarction (MI) and premature death, thus, mimicking human disease fairly well. However, these mice, except PDZK1, also exhibit abnormally high ratio of unesterified to total cholesterol (UC:TC), resulting in infertility. This makes the mouse model difficult to raise or produce and very costly. Even though PDZK1 mice are fertile, these mice in combination with apoE knockout (KO) develop CHD that is substantially less severe than other models. Thus, there is a huge need to develop a mouse model of atherosclerotic CHD that captures all the phenotype but is still fertile.