GENETIC-ANALYSIS OF THE DIFFERENCE IN DIET-INDUCED ATHEROSCLEROSIS BETWEEN THE INBRED MOUSE STRAINS SM J AND NZB/B1NJ/

To identify the genetic factors affecting susceptibility to atheroscle rosis, we studied the inheritance of plasma total cholesterol (TC) and HDL cholesterol (HDL-C) concentrations and susceptibility to atherosc lerotic lesion formation in an (SM/J[SM] xNZB/B1NJ[NZB]) outcross, an (SMXNZB)F1[F1]xSM backcross, and the NXSM recombinant inbred (RI) stra in set. After 18 or 26 weeks on the atherogenic diet, lesion sizes in female mice were 160+/-110 (SE) mu m(2) for NZB, 100+/-60 for F1, and 3800+/-920 for SM. After 0, 4, or 26 weeks on the atherogenic diet, NZ B 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 pa rent, 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 S M, and 4 were intermediate between NZB and SM for lesion size. For the (SMXNZB)F1XSM backcross offspring, 26 resembled NZB and F1, 7 resembl ed SM, and 6 were intermediate between NZB and SM for lesion size. The re was poor correlation between lesion size and plasma TC or HDL-C in the parental strains and the backcross. These data suggest that resist ance to atherosclerosis is determined by at least one major dominant g ene contributed by the NZB strain, which we have named Ath8. Ath8 segr egates independently of genes controlling TC and HDL-C levels.