Submitted on May 10, 2006
Revised on July 13, 2006
Accepted on July 13, 2006
Plasma plant sterol locus on mouse chromosome 14 confirmed in congenics and subcongenics reveals a complex locus with at least 2 genes regulating intestinal sterol absorption
Ephraim Sehayek, Yee Yan Fung, Hannah J. Yu, Jan Lembcke, Uta Ceglarek, Daniel Teupser, Joachim Thiery, Dieter Lutjohann, Klaus von Bergmann, and Jan L. Breslow
Laboratory of Biochemical Genetics and Metabolism, The Rockefeller University, New York, NY 10021
Corresponding Author: sehayee{at}rockefeller.edu
We previously identified two inbred mouse strains, C57BL/6J and castaneus (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 17cM with a maximum LOD score of 9.9. Studies in a chromosome 14 congenic strain, 14KK, with a 4-60cM 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 4-19.5cM and 19.5–60cM CASA/Rk intervals, respectively, both males and females had decreased plasma plant sterol levels and decreased intestinal cholesterol absorption. Compatible with decreased plasma plant sterol phenotype, 14PKK mice had increased biliary plant sterol excretion, whereas 14DKK mice did not. Therefore, gender dependent interaction 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 2 sets of genes operating; one set affecting intestinal sterol absorption and biliary excretion and the other mainly affecting intestinal sterol absorption.
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