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Journal of Lipid Research, Vol. 42, 1812-1819, November 2001
Copyright © 2001 by Lipid Research, Inc.

Genetic analysis of cholesterol accumulation in inbred mice

Correspondence to: David W. Russell, To whom correspondence should be addressed., russell{at}utsw.swmed.edu (E-mail)

Genetic linkage analysis in the laboratory mouse identified chromosomal regions containing genes that contribute to cholesterol accumulation in the liver and plasma. Comparisons between five inbred strains of mice obtained from the Jackson Laboratory (DBA/2, AKR, C57BL/6, SJL, and 129P3) revealed a direct correlation between intestinal cholesterol absorption and susceptibility to diet-induced hypercholesterolemia. This correlation was lost in the F₁ generation arising from crosses between high- and low-absorbing strains. Linkage analyses in AKxD recombinant inbred strains and 129xSJL129F₁ N₂ backcross mice identified four quantitative trait loci (QTL) that influenced Liver cholesterol accumulation (Lcho1–4) and one locus that affected Plasma cholesterol accumulation (Pcho1). These loci map to five chromosomes and, with one exception, are different from the seven QTL identified previously that influence intestinal cholesterol absorption.

We conclude that a large number of genes affects the amount of cholesterol absorbed in the small intestine and its accumulation in the liver and plasma of inbred mice. — Schwarz, M., D. L. Davis, B. R. Vick, and D. W. Russell. Genetic analysis of cholesterol accumulation in inbred mice. J. Lipid Res. 2001. 42: 1812–1819.

Supplementary key words: quantitative trait mapping, lipid metabolism, liver cholesterol, plasma cholesterol, bile acids, cholesterol absorption

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