Quantitative trait loci analysis for the differences in susceptibility to atherosclerosis and diabetes between inbred mouse strains C57BL/6J and C57BLKS/J

Mice from the inbred strain C57BLKS/J (BKS) exhibit increased susceptibilit y to both diabetes and atherosclerosis compared to C57BL/6J (B6) mice. To d etermine whether the differences in diabetes and atherosclerosis are relate d, we carried out a cross between B6-db/db and BKS, We selected 99 female F -2-db/db progeny, tested the progeny for plasma lipids, plasma glucose, and fatty-streak lesions, and used quantitative trait loci (QTL) analysis to i dentify the chromosomal regions associated with these phenotypes, No major QTL were found for total cholesterol, VLDL-G cholesterol, or triglycerides. Two suggestive QTL were found for HDL-cholesterol (LOD scores of 2.7 and 2 .8), and two suggestive loci were found for plasma glucose (LOD scores of 2 .3 and 2.0). Lesion size was not correlated with plasma lipid levels or glu cose. Lesion size was determined by a locus at D12Mit49 with a LOD score of 2.5 and a significant likelihood ratio statistic. The gene for apolipoprot ein apoB lies within the region, but apoB levels were similar in strains B6 and BKS, The QTL on Chr 12 was confirmed by constructing a congenic strain with BKS alleles in the QTL region on a B6 genetic backgound. We conclude that susceptibilities to diabetes and atherosclerosis are not conferred by the same genes in these strains and that a major gene on Chr 12, which we n ame Ath6, determines the difference in atherosclerosis susceptibility.