Quantitative Trait Locus Analysis of Neointimal Formation in an Intercross Between C57BL/6 and C3H/HeJ Apolipoprotein E-Deficient Mice

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 F1s, which were intercrossed to generate 204 male F-2 progeny. At 10 weeks of age, F(2)s underwent endothelium denudation injury to the left common carotid artery. Mice were fed a Western 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. (Circ Cardiovasc Genet. 2009; 2: 220-228.)