An
animal model of
coronary heart disease has been developed where myocardial infarct can be induced by altering the animal's diet. In all embodiments, this
animal model is a result of reduced activity of
scavenger receptor class BI (SR-BI) and apolipoprotein E (ApoE). In a preferred embodiment, the model is a result of crossbreeding two transgenic mouse lines: a knockout of SR-BI (SR-BI− / −) and an impaired ApoE expressor (hypoE). The impaired ApoE
gene results in only 2-5% expression of ApoE and a reduction in
cholesterol homeostasis. Resulting animals are predisposed to hypercholesterolemia but can live longer than a year on a normal low
fat diet.
Serum plasma levels can be significantly elevated by changing the animal's diet to one containing high levels of fat and
cholesterol. Within a month on a
high fat,
high cholesterol diet, animals develop atherosclerosis and
myocardial infarction occurs. Survival depends on the nature of the diet and the conditions of
animal husbandry and can typically be around 20-30 days after administration of the modified diet depending on the specific conditions. Housing the animals alone or in groups significantly affects survival of these animals on a
high fat diet. Analysis of B- and T-
cell deficient SR-BI / ApoE / RAG2 triple knockout mice established that B- and T-lymphocytes do not play a key role in the
pathophysiology of the SR-BI ApoE dKO model of
human disease. These animal models can be used to study mechanisms and progression of CHD as a function of diet, treatment with drugs to be screened for
efficacy or undesirable side effects, and social environmental effects.