Nature Medicine
4, 934 - 938 (1998)
doi:10.1038/nm0898-934
There is an Erratum (October 1998) associated with this Article.
A mouse model of human familial hypercholesterolemia: Markedly elevated low density lipoprotein cholesterol levels and severe atherosclerosis on a low-fat chow dietLyn Powell-Braxton1, Murielle Véniant2, Richard D. Latvala1, Ken-Ichi Hirano3, Wesley B. Won1, Jed Ross1, Noel Dybdal1, Constance H. Zlot2, Stephen G. Young2
& Nicholas O. Davidson3, 4, 5
1Cardiovascular Research, Genentech Inc., South San Francisco, California 94080
2Gladstone Institute of Cardiovascular Disease, Department of Medicine, and the Cardiovascular Research Institute, University of California, San Francisco, California 941
3Department of Medicine, University of Chicago, Chicago, Illinois 60637
4Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110
5Correspondence should be addressed to N.O.D.; email: ndavidso@medicine.bsd.uchicago.edu 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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