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A mouse model of human familial hypercholesterolemia: Markedly elevated low density lipoprotein cholesterol levels and severe atherosclerosis on a low-fat chow diet

Nature Medicine volume 4, pages 934–938 (1998)Cite this article

An Erratum to this article was published on 01 October 1998

Abstract

Mutations in the low density lipoprotein (LDL) receptor gene cause familial hypercholesterolemia, a human disease characterized by premature atherosclerosis and markedly elevated plasma levels of LDL cholesterol and apolipoprotein (apo) B100. In contrast, mice deficient for the LDL receptor (Ldlr−/−) have only mildly elevated LDL cholesterol levels and little atherosclerosis. This difference results from extensive editing of the hepatic apoB mRNA in the mouse, which limits apoB100 synthesis in favor of apoB48 synthesis. We have generated Ldlr−/− mice that cannot edit the apoB mRNA and therefore synthesize exclusively apoBIOO. These mice had markedly elevated LDL cholesterol and apoBIOO levels and developed extensive atherosclerosis on a chow diet. This authentic model of human familial hypercholesterolemia will provide a new tool for studying atherosclerosis.

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Authors and Affiliations

  1. Cardiovascular Research, Genentech Inc., South San Francisco, California, 94080

    Lyn Powell-Braxton, Richard D. Latvala, Wesley B. Won, Jed Ross & Noel Dybdal

  2. Gladstone Institute of Cardiovascular Disease, Department of Medicine, and the Cardiovascular Research Institute, University of California, San Francisco, California, 941

    Murielle Véniant, Constance H. Zlot & Stephen G. Young

  3. Department of Medicine, University of Chicago, Chicago, Illinois, 60637

    Ken-Ichi Hirano & Nicholas O. Davidson

  4. Department of Medicine, Washington University School of Medicine, St. Louis, MO, 63110

    Nicholas O. Davidson

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  1. Lyn Powell-Braxton
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Correspondence to Nicholas O. Davidson.

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Powell-Braxton, L., Véniant, M., Latvala, R. et al. A mouse model of human familial hypercholesterolemia: Markedly elevated low density lipoprotein cholesterol levels and severe atherosclerosis on a low-fat chow diet. Nat Med 4, 934–938 (1998). https://doi.org/10.1038/nm0898-934

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  • DOI: https://doi.org/10.1038/nm0898-934

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