J. Lipid Res.
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Originally published In Press as doi:10.1194/jlr.M600202-JLR200 on July 13, 2006

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Journal of Lipid Research, Vol. 47, 2291-2296, October 2006
Copyright © 2006 by American Society for Biochemistry and Molecular Biology

A complex plasma plant sterol locus on mouse chromosome 14 has at least two genes regulating intestinal sterol absorption

Ephraim Sehayek1,*, Yee Yan Fung*, Hannah J. Yu*, Jan Lembcke{dagger}, Uta Ceglarek{dagger}, Daniel Teupser{dagger}, Joachim Thiery{dagger}, Dieter Lutjohann§, Klaus von Bergmann§ and Jan L. Breslow*

* Laboratory of Biochemical Genetics and Metabolism, The Rockefeller University, New York, NY
{dagger} Institute of Laboratory Medicine, Clinical Chemistry, and Molecular Diagnostics, University Hospital, Leipzig, Germany
§ Department of Clinical Pharmacology, University of Bonn, Bonn, Germany

Published, JLR Papers in Press, July 13, 2006.

1 To whom correspondence should be addressed. e-mail: sehayee{at}rockefeller.edu (E.S.)

We previously identified two inbred mouse strains, C57BL/6J and CASA/Rk, with different plasma plant sterol levels. An intercross between these strains revealed a broad plasma plant sterol locus on chromosome 14, which peaked at 17 centimorgan (cM) with a maximum logarithm of the odds score of 9.9. Studies in a chromosome 14 congenic strain, 14KK, with a 4–60 cM CASA/Rk interval on the C57BL/6J background revealed that males, but not females, had decreased plasma plant sterol levels and intestinal cholesterol absorption. In two subcongenic strains, 14PKK and 14DKK, with 4–19.5 and 19.5–60 cM CASA/Rk intervals, respectively, both males and females had decreased plasma plant sterol levels and decreased intestinal cholesterol absorption. Compatible with the decreased plasma plant sterol phenotype, 14PKK mice had increased biliary plant sterol excretion, whereas 14DKK mice did not. Therefore, gender-dependent interactions of genes at the 14PKK and 14DKK intervals are likely to underlie the 14KK interval effect on plasma plant sterol levels and sterol absorption from the intestine. These studies confirm the plasma plant sterol locus on mouse chromosome 14 and provide evidence that there are at least two sets of genes operating: one set affecting intestinal sterol absorption and biliary excretion, and the other set mainly affecting intestinal sterol absorption.

Supplementary key words cholesterol absorption • bile • genetics

Abbreviations: cM, centimorgan; LOD, logarithm of the odds


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