A complex plasma plant sterol locus on mouse chromosome 14 has at least two genes regulating intestinal sterol absorption.
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.
Sehayek
Ephraim
E
Laboratory of Biochemical Genetics and Metabolism, The Rockefeller University, New York, NY, USA. sehayee@rockefeller.edu
Fung
Yee Yan
YY
Yu
Hannah J
HJ
Lembcke
Jan
J
Ceglarek
Uta
U
Teupser
Daniel
D
Thiery
Joachim
J
Lutjohann
Dieter
D
von Bergmann
Klaus
K
Breslow
Jan L
JL
D000818:Animals; D020296:Animals, Congenic; D002874:Chromosome Mapping; D033481:Chromosomes, Mammalian / Q000235:genetics*; D005260:Female; D005838:Genotype; D007408:Intestinal Absorption / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010840:Phytosterols / Q000097:blood* / Q000378:metabolism* / Q000493:pharmacokinetics; D013045:Species Specificity
D010840:Phytosterols