Genetics of responsiveness to high-fat and high-cholesterol diets in the mouse.

The natural variation among inbred strains of mice was used to elucidate the genetic factors underlying the responsiveness to high-fat and high-cholesterol diets. The nine strains examined are the progenitors of recombinant inbred strain sets: C57BL/6J, C57L/J, SWR/J, SJL/J, SM/J, A/J, AKR/J, C3H/HeJ, and DBA/2J. Plasma lipids, liver lipids, the prevalence of cholesterol gallstones, and the size of aortic fatty streak lesions were examined after 18 wk of consumption of the diet containing 15% fat and 1% cholesterol. The variation in aortic lesions found among inbred strains provided the basis for several additional studies that demonstrated the existence of eight genes affecting atherosclerosis. These genes, named Ath1 to Ath8, are briefly described. The genetic analysis of variation in gallstone formation demonstrated that more than one gene affects this phenotype.