Published Online
on April 21, 2009

A more recent version of this article appeared on June 1, 2009

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Original Article

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

Zuobiao Yuan; Hong Pei; Drew J. Roberts; Zhimin Zhang; Jessica S. Rowlan; Alan H. Matsumoto and Weibin Shi¹

University of Virginia, Charlottesville, VA

¹ E-mail: ws4v{at}virginia.edu

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 (QTL) 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 F₂ progeny. At 10 weeks of age, F₂s 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 MCP-1 levels. One significant QTL, named Nih1 (61cM, LOD score: 5.02), on chromosome 12 and a suggestive locus on chromosome 13 (35cM, LOD: 2.67) were identified to influence lesion size. One significant QTL on distal chromosome 1 accounted for major variations in plasma non-HDL cholesterol and triglyceride levels. Four suggestive QTLs 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.

Key Words: atherosclerosis • calcium • endocardium • hypercholesterolemia • restenosis • mice • neointimal hyperplasia • quantitative trait locus