J. Lipid Res.
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Journal of Lipid Research, Vol. 42, 1801-1811, November 2001
Copyright © 2001 by Lipid Research, Inc.

Genetic analysis of intestinal cholesterol absorption in inbred mice

Margrit Schwarza, Daphne L. Davisa, Bertrand R. Vicka, and David W. Russella
a Department of Molecular Genetics, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9046

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

A genetic mapping strategy was employed to identify chromosomal regions harboring genes that influence the absorption of intestinal cholesterol in the mouse. Analysis of seven inbred strains of male mice (129P3, AKR, BALB/c, C3H/He, C57BL/6, DBA/2, and SJL, all from Jackson Laboratories) revealed substantial differences in their abilities to absorb a bolus of cholesterol delivered by gavage. Crosses between high (AKR, 129) and low (DBA/2, SJL) absorbing strains revealed evidence for the presence of dominant genes that increase and decrease cholesterol absorption. Backcrosses between F1 offspring and parental strains (DBA/2xAKD2F1 and 129xSJL129F1) followed by linkage analyses revealed four quantitative trait loci that influenced cholesterol absorption. Analyses of recombinant inbred strains identified an additional three loci affecting this phenotype.

These seven quantitative trait loci, which map to different chromosomes and are termed Cholesterol absorption 1–7 (Chab1–7) loci, together influence the absorption of intestinal cholesterol in mice and are likely to be involved in different steps of this complex pathway. — Schwarz, M., D. L Davis, B. R. Vick, and D. W. Russell. Genetic analysis of intestinal cholesterol absorption in inbred mice. J. Lipid Res. 2001. 42: 1801–1811.

Supplementary key words: quantitative trait mapping, lipid metabolism, bile acids


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