Massive xanthomatosis and atherosclerosis in cholesterol-fed low density lipoprotein receptor-negative mice

Research output: Contribution to journalArticle

556 Scopus citations

Abstract

Mice that are homozygous for a targeted disruption of the LDL receptor gene (LDLR(-/-) mice) were fed a diet that contained 1.25% cholesterol, 7.5% cocoa butter, 7.5% casein, and 0.5% cholic acid. The total plasma cholesterol rose from 246 to > 1,500 mg/dl, associated with a marked increase in VLDL, intermediate density lipoproteins (IDL), and LDL cholesterol, and a decrease in HDL cholesterol. In wild type littermates fed the same diet, the total plasma cholesterol remained < 160 mg/dl. After 7 mo, the LDLR(-/-) mice developed massive xanthomatous infiltration of the skin and subcutaneous tissue. The aorta and coronary ostia exhibited gross atheromata, and the aortic valve leaflets were thickened by cholesterol-laden macrophages. No such changes were seen in the LDLR(-/-) mice on a normal chow diet, nor in wild type mice that were fed either a chow diet or the high-fat diet. We conclude that LDL receptors are largely responsible for the resistance of wild type mice to atherosclerosis. The cholesterol-fed LDLR(-/-) mice offer a new model for the study of environmental and genetic factors that modify the processes of atherosclerosis and xanthomatosis.

Original languageEnglish (US)
Pages (from-to)1885-1893
Number of pages9
JournalJournal of Clinical Investigation
Volume93
Issue number5
DOIs
StatePublished - May 1994

Keywords

  • animal model for atherosclerosis
  • hypercholesterolemia
  • lipoprotein metabolism
  • liver receptors
  • targeted gene disruption

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint Dive into the research topics of 'Massive xanthomatosis and atherosclerosis in cholesterol-fed low density lipoprotein receptor-negative mice'. Together they form a unique fingerprint.

  • Cite this