| Hypercholesterolemia and atherosclerosis in low density lipoprotein receptor mutant rats. | |
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MedLine Citation:
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PMID: 22293196 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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To establish low density lipoprotein receptor (LDLR) mutant rats as a hypercholesterolemia and atherosclerosis model, we screened the rat LDLR gene for mutations using an N-ethyl-N-nitrosourea mutagenesis archive of rat gene data, and identified five mutations in its introns and one missense mutation (478T>A) in exon 4. The C160S mutation was located in the ligand binding domain of LDLR and was revealed to be equivalent to mutations (C160Y/G) identified in human familial hypercholesterolemia (FH) patients. The wild type, heterozygous, and homozygous mutant rats were fed a normal chow diet or a high fat high cholesterol (HFHC) diet from the age of 10weeks for 16weeks. The LDLR homozygous mutants fed the normal chow diet showed higher levels of plasma total cholesterol and LDL cholesterol than the wild type rats. When fed the HFHC diet, the homozygous mutant rats exhibited severe hyperlipidemia and significant lipid deposition from the aortic arch to the abdominal aorta as well as in the aortic valves. Furthermore, the female homozygous mutants also developed xanthomatosis in their paws. In conclusion, we suggest that LDLR mutant rats are a useful novel animal model of hypercholesterolemia and atherosclerosis. |
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Authors:
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Makoto Asahina; Tomoji Mashimo; Michiyasu Takeyama; Ryuichi Tozawa; Tadatoshi Hashimoto; Akiko Takizawa; Masatsugu Ueda; Toshihiro Aoto; Takashi Kuramoto; Tadao Serikawa |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-1-24 |
Journal Detail:
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Title: Biochemical and biophysical research communications Volume: - ISSN: 1090-2104 ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-2-1 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0372516 Medline TA: Biochem Biophys Res Commun Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2012. Published by Elsevier Inc. |
Affiliation:
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Takeda Pharmaceutical Company Ltd., Pharmaceutical Research Division, Kanagawa, Japan. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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