A mouse model of human familial hypercholesterolemia: Markedly elevated low density lipoprotein cholesterol levels and severe atherosclerosis on a low-fat chow diet
| Autor: | Wesley Won, Lyn Powell-Braxton, Richard D. Latvala, Stephen G. Young, Murielle M. Véniant, Nicholas O. Davidson, Constance H. Zlot, Noel Dybdal, Ken-Ichi Hirano, Jed Ross |
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| Rok vydání: | 1998 |
| Předmět: |
Male
Apolipoprotein E medicine.medical_specialty Apolipoprotein B Arteriosclerosis Aorta Thoracic Familial hypercholesterolemia Muscle Smooth Vascular General Biochemistry Genetics and Molecular Biology Hyperlipoproteinemia Type II Mice chemistry.chemical_compound Internal medicine medicine Animals Humans RNA Messenger Diet Fat-Restricted Crosses Genetic Triglycerides Apolipoproteins B Mice Knockout Sex Characteristics biology Cholesterol business.industry nutritional and metabolic diseases Cholesterol LDL General Medicine medicine.disease Disease Models Animal Endocrinology Liver Receptors LDL chemistry Low-density lipoprotein LDL receptor biology.protein Female lipids (amino acids peptides and proteins) RNA Editing business |
| Zdroj: | Nature Medicine. 4:934-938 |
| ISSN: | 1546-170X 1078-8956 |
| DOI: | 10.1038/nm0898-934 |
| Popis: | 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 apoB100. These 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. |
| Databáze: | OpenAIRE |
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