Genetic Analysis of the Difference in Diet-Induced Atherosclerosis Between the Inbred Mouse Strains SM/J and NZB/BlNJ

Abstract—To identify the genetic factors affecting susceptibility to atherosclerosis, we studied the inheritance of plasma total cholesterol (TC) and HDL cholesterol (HDL-C) concentrations and susceptibility to atherosclerotic lesion formation in an (SM/J[SM]×NZB/BlNJ[NZB]) outcross, an (SM×NZB)F1[F1]×SM backcross, and the NXSM recombinant inbred (RI) strain set. After 18 or 26 weeks on the atherogenic diet, lesion sizes in female mice were 160±110 (SE) μm2 for NZB, 100±60 for F1, and 3800±920 for SM. After 0, 4, or 26 weeks on the atherogenic diet, NZB had higher TC and HDL-C levels than either SM or F1. The F1 progeny had TC and HDL-C levels slightly higher than or similar to the SM/J parent, while lesion size in the F1 progeny was more similar to the NZB parent. Among the 15 RI strains, 8 resembled NZB and F1, 3 resembled SM, and 4 were intermediate between NZB and SM for lesion size. For the (SM×NZB)F1×SM backcross offspring, 26 resembled NZB and F1, 7 resembled SM, and 6 were intermediate between NZB...