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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:597.)
© 2006 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Atherosclerosis Susceptibility Loci Identified From a Strain Intercross of Apolipoprotein E–Deficient Mice via a High-Density Genome Scan

Jonathan D. Smith; Jeffrey M. Bhasin; Julie Baglione; Megan Settle; Yaomin Xu; John Barnard

From the Departments of Cell Biology (J.D.S., J.M.B., J.B., M.S.), Cardiovascular Medicine (J.D.S.), and Quantitative Health Sciences (Y.X., J.Barnard), Cleveland Clinic Foundation, Cleveland Ohio; and the Department of Molecular Medicine (J.D.S.), Case School of Medicine, Cleveland Ohio.

Correspondence to Jonathan D. Smith, Department of Cell Biology, NC10, The Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195. E-mail smithj4{at}ccf.org

Objective— Apolipoprotein (apo) E-deficient mice are hypercholesterolemic and develop atherosclerosis on low-fat chow diets; however, the genetic background strain has a large effect on atherosclerosis susceptibility. This study aimed to determine the genetic regions associated with strain effects on lesion area.

Methods and Results— We performed a strain intercross between atherosclerosis sensitive DBA/2 and atherosclerosis resistant AKR apoE-deficient mice. Aortic root lesion area, total cholesterol, body weights, and complete blood counts were ascertained for 114 male and 95 female F₂ progeny. A high-density genome scan was performed using a mouse single nucleotide polymorphism chip yielding 1967 informative polymorphic markers. Quantitative trait locus (QTL) statistical analyses were performed. Novel loci associated with lesion or log lesion area were identified for the female and male F₂ cohorts. The atherosclerosis QTLs in female mice reside on chromosomes 15, 5, 3, and 13, and in male mice on chromosomes 17, 18, and 2. QTL were also identified for body weight, total cholesterol, and blood count parameters.

Conclusions— Loci were identified for atherosclerosis susceptibility in a strain intercross study. The identity of the responsible genes at these loci remains to be determined.

A strain intercross was performed between atherosclerosis sensitive DBA/2 and atherosclerosis resistant AKR apoE-deficient mice. Aortic root lesion area was ascertained for male and female F₂ progeny. A high-density genome scan was performed using single-nucleotide polymorphism chips. Quantitative trait locus statistical analyses identified novel loci associated atherosclerosis susceptibility.

Key Words: atherosclerosis • mouse genetics • quantitative trait locus • QTL

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