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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2009;29:47.)
© 2009 American Heart Association, Inc.

Integrative Physiology/Experimental Medicine

Genetic Modifier Loci Linked to Intima Formation Induced by Low Flow in the Mouse Carotid

Vyacheslav A. Korshunov; Bradford C. Berk

From the Aab Cardiovascular Research Institute and Department of Medicine, University of Rochester School of Medicine and Dentistry, NY.

Correspondence to Vyacheslav "Slava" A. Korshunov, Aab Cardiovascular Research Institute, 601 Elmwood Avenue, Rochester, NY 14642. E-mail Slava_Korshunov{at}URMC.rochester.edu

Objective— Previously we found dramatic strain-dependent differences in a low flow model of vascular remodeling. Specifically, intima formation in the left common carotid artery was 30-fold greater in SJL compared to C3HeB/Fe (C3H/F) mice. We hypothesized that a few genes control intima formation in response to low flow. A C3H/F and SJL backcross resulted in broad range of N2 intima phenotypes.

Methods and Results— Using genome-wide scan we identified two highly significant quantitative trait loci (QTLs) for intima, Im1 (intima modifier 1 locus) on chromosome 2 (Chr2; 77.6 cM, LOD=6.4), and Im2 on Chr11 (17 cM, LOD=5.3). One significant QTL Im3 was found on Chr18 (6 cM, LOD=3.0), and two suggestive QTLs (LOD=1.5 and 1.8) were identified on Chr7 and Chr17, respectively. Interestingly, the intima/media ratio trait mapped to the same QTLs as the intima trait. Haplotype mapping predicted 40 candidate genes. Six of these genes contained SNPs that differed between C3H/F and SJL.

Conclusions— We have successfully mapped 3 QTLs (Im1, Im2, and Im3) that are associated with carotid intima formation in response to low blood flow. These results may be important in identifying genes that influence carotid intima-media thickening and predict cardiovascular disease in humans.

Genetic analysis of intima formation in response to low blood flow was studied in a backcross between 2 inbred mouse strains. For the first time we identified 3 quantitative trait loci that contribute to intima thickening in the mouse carotid.

Key Words: genetics • intima • low blood flow • mouse • SJL/J • C3HeB/FeJ