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Journal of Lipid Research, Vol. 41, 573-582, April 2000
Copyright © 2000 by Lipid Research, Inc.

Original Article

A locus conferring resistance to diet-induced hypercholesterolemia and atherosclerosis on mouse chromosome 2

Aram Mouzeyana, Junghee Choif, Hooman Allayeea, Xuping Wangb, Janet Sinsheimerc, Jack Phane, Lawrence W. Castellanib, Karen Reueb,e, Aldons J. Lusisa,b,d, and Richard C. Davisb
a Departments of Microbiology and Molecular Genetics, University of California, Los Angeles, CA 90095
b Medicine/Cardiology Division, University of California, Los Angeles, CA 90095
c Biomathematics, University of California, Los Angeles, CA 90095
d Molecular Biology Institute, University of California, Los Angeles, CA 90095
e Lipid Research Laboratory, VA West Los Angeles Healthcare Center, Los Angeles, CA 90073
f Department of Food and Nutrition, Seoul National University, Seoul, South Korea

Correspondence to: Richard C. Davis

Dietary cholesterol is known to raise total and low density lipoprotein cholesterol concentrations in humans and experimental animals, but the response among individuals varies greatly. Here we describe a mouse strain, C57BL/6ByJ (B6By), that is resistant to diet-induced hypercholesterolemia, in contrast to the phenotype seen in other common strains of mice including the closely related C57BL/6J (B6J) strain. Compared to B6J, B6By mice exhibit somewhat lower basal cholesterol levels on a chow diet, and show a relatively modest increase in absolute levels of total and LDL/VLDL cholesterol in response to an atherogenic diet containing 15% fat, 1.25% cholesterol, and 0.5% cholate. Correspondingly, B6By mice are also resistant to diet-induced aortic lesions, with less than 15% as many lesions as B6J. Food intake and cholesterol absorption are similar between B6By and B6J mice.

To investigate the gene(s) underlying the resistant B6By phenotype, we performed genetic crosses with the unrelated mouse strain, A/J. A genome-wide scan revealed a locus, designated Diet1, on chromosome 2 near marker D2Mit117 showing highly significant linkage (lod = 9.6) between B6By alleles and hypo-response to diet. Examination of known genes in this region suggested that this locus represents a novel gene affecting plasma lipids and atherogenesis in response to diet.—Mouzeyan, A., J. Choi, H. Allayee, X. Wang, J. Sinsheimer, J. Phan, L. W. Castellani, K. Reue, A. J. Lusis, and R. C. Davis. A locus conferring resistance to diet-induced hypercholesterolemia and atherosclerosis on mouse chromosome 2. J. Lipid Res. 2000. 41: 573;–582.

Supplementary key words: chromosomes/GENETICS, quantitative trait, chromosome mapping, animal, mice, inbred strains, hyperlipidemia/*GENETICS, cholesterol/BLOOD, atherosclerosis/DIET


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