Journal of Lipid Research (Apr 2000)

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

  • Aram Mouzeyan,
  • Junghee Choi,
  • Hooman Allayee,
  • Xuping Wang,
  • Janet Sinsheimer,
  • Jack Phan,
  • Lawrence W. Castellani,
  • Karen Reue,
  • Aldons J. Lusis,
  • Richard C. Davis

Journal volume & issue
Vol. 41, no. 4
pp. 573 – 582

Abstract

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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 hyporesponse 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.

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