Quantitative trait locus analysis of neointimal formation in an intercross between C57BL/6 and C3H/HeJ apolipoprotein E-deficient mice

Abstract

Background-Inbred mouse strains C57BL/6J (B6) and C3H/HeJ (C3H) exhibit marked differences in neointimal formation after arterial injury when deficient in apolipoprotein E (apoE-/-) and fed a Western diet. Quantitative trait locus analysis was performed on an intercross between B6.apoE -/- and C3H.apoE-/- mice to determine genetic factors contributing to the phenotype. Methods and Results-Female B6.apoE-/- mice were crossed with male C3H.apoE-/- mice to generate F 1s, which were intercrossed to generate 204 male F2 progeny. At 10 weeks of age, F2s underwent endothelium denudation injury to the left common carotid artery. Mice were fed aWestern diet for 1 week before and 4 weeks after injury and analyzed for neointimal lesion size, plasma lipid, and membrane cofactor protein (MCP)-1 levels. One significant quantitative trait locus, named Nih1 (61 cM; LOD score, 5.02), on chromosome 12 and a suggestive locus on chromosome 13 (35 cM; LOD score, 2.67) were identified to influence lesion size. One significant quantitative trait locus on distal chromosome 1 accounted for major variations in plasma non-high-density lipoprotein cholesterol and triglyceride levels. Four suggestive quantitative trait locis on chromosomes 1, 2, and 3 were detected for circulating MCP-1 levels. No correlations were observed between neointimal lesion size and plasma lipid levels or between lesion size and plasma MCP-1 levels. Conclusions-Neointimal formation is controlled by genetic factors independent of those affecting plasma lipid levels and circulating MCP-1 levels in the B6 and C3H mouse model. © 2009 American Heart Association, Inc.