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AssigneeThe J. David Gladstone Institutes
InventorsRobert Raffai, Karl Weisgraber
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An animal model has been developed where the animals can survive myocardial infarctions caused by diet-induced coronary atherosclerosis, and live with chronic heart failure. This animal model is a result of reduced activity of scavenger receptor class BI (SR-BI) and ApoE and the inducible activity of the Mx1-Cre gene. In a preferred embodiment, the model is a result of crossbreeding two transgenic mouse lines: a knockout of SR-BI (SRBI−/−) and an impaired ApoE expressor (Apoeh/h) to generate a strain referred to as Apoeh/hSRB1−/− mice, which is then crossbred to mice that carry the inducible Mx1-Cre transgene. The Apoeh/hSRB1−/− mouse model is genetically modified, enabling the offspring to rapidly and permanently lower their high blood cholesterol levels caused by dietary challenge. The ability to rapidly and permanently lower blood cholesterol levels in these mice stops and may cause the regression of occlusive coronary atherosclerosis restoring blood flow to the heart, allowing the mice to survive from myocardial infarction and live with chronic heart failure.
An animal model of coronary heart disease wherein a heart attack can be induced by feeding a lipid enriched diet, comprising an animal with decreased SR-BI and apolipoprotein activities, wherein there is at least some activity of either the SR-BI or the apolipoprotein, and a promoter which causes temporal and spatial, temporally and/or spatially regulated gene deletion.
Dependencies are inferred from the claim text.