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

Lyn Powell-Braxton; Murielle Véniant; Richard D. Latvala; Ken Ichi Hirano; Wesley B. Won; Jed Ross; Noel Dybdal; Constance H. Zlot; Stephen G. Young; Nicholas O. Davidson

doi:10.1038/nm0898-934

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

Lyn Powell-Braxton, Murielle Véniant, Richard D. Latvala, Ken Ichi Hirano, Wesley B. Won, Jed Ross, Noel Dybdal, Constance H. Zlot, Stephen G. Young, Nicholas O. Davidson

Research output: Contribution to journal › Article › peer-review

198 Scopus citations

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 threfore synthesize exclusively apoB100. This mice had markedly elevated LDL cholesterol and apoB100 levels and developed extensive atherosclerosis on a chow diet. This authentic model of human familial hypercholesterolemia will provide a new tool for studying atherosclerosis.

Original language	English
Pages (from-to)	934-938
Number of pages	5
Journal	Nature medicine
Volume	4
Issue number	8
DOIs	https://doi.org/10.1038/nm0898-934
State	Published - Aug 1998

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Powell-Braxton, L., Véniant, M., Latvala, R. D., Hirano, K. I., Won, W. B., Ross, J., Dybdal, N., Zlot, C. H., Young, S. G., & Davidson, N. O. (1998). 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, 4(8), 934-938. https://doi.org/10.1038/nm0898-934

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

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 threfore synthesize exclusively apoB100. This mice had markedly elevated LDL cholesterol and apoB100 levels and developed extensive atherosclerosis on a chow diet. This authentic model of human familial hypercholesterolemia will provide a new tool for studying atherosclerosis.",

author = "Lyn Powell-Braxton and Murielle V{\'e}niant and Latvala, {Richard D.} and Hirano, {Ken Ichi} and Won, {Wesley B.} and Jed Ross and Noel Dybdal and Zlot, {Constance H.} and Young, {Stephen G.} and Davidson, {Nicholas O.}",

year = "1998",

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doi = "10.1038/nm0898-934",

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Powell-Braxton, L, Véniant, M, Latvala, RD, Hirano, KI, Won, WB, Ross, J, Dybdal, N, Zlot, CH, Young, SG & Davidson, NO 1998, '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, vol. 4, no. 8, pp. 934-938. https://doi.org/10.1038/nm0898-934

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T2 - Markedly elevated low density lipoprotein cholesterol levels and severe atherosclerosis on a low-fat chow diet

AU - Powell-Braxton, Lyn

AU - Véniant, Murielle

AU - Latvala, Richard D.

AU - Hirano, Ken Ichi

AU - Won, Wesley B.

AU - Ross, Jed

AU - Dybdal, Noel

AU - Zlot, Constance H.

AU - Young, Stephen G.

AU - Davidson, Nicholas O.

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AB - 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 threfore synthesize exclusively apoB100. This mice had markedly elevated LDL cholesterol and apoB100 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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JO - Nature medicine

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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

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