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Hypercholesterolemia and atherosclerosis in low density lipoprotein receptor mutant rats.

Authors: Asahina, Makoto  Mashimo, Tomoji  Takeyama, Michiyasu  Tozawa, Ryuichi  Hashimoto, Tadatoshi  Takizawa, Akiko  Ueda, Masatsugu  Aoto, Toshihiro  Kuramoto, Takashi  Serikawa, Tadao 
Citation: Asahina M, etal., Biochem Biophys Res Commun. 2012 Feb 17;418(3):553-8. doi: 10.1016/j.bbrc.2012.01.067. Epub 2012 Jan 24.
Pubmed: (View Article at PubMed) PMID:22293196
DOI: Full-text: DOI:10.1016/j.bbrc.2012.01.067

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 10 weeks for 16 weeks. 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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RGD ID: 12910105
Created: 2017-06-08
Species: All species
Last Modified: 2017-06-08
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.