出版社:American Society for Biochemistry and Molecular Biology
摘要:We previously identified two inbred mouse strains, C57BL/6Jand CASA/Rk, with different plasma plant sterol levels. An intercrossbetween these strains revealed a broad plasma plant sterol locuson chromosome 14, which peaked at 17 centimorgan (cM) with amaximum logarithm of the odds score of 9.9. Studies in a chromosome14 congenic strain, 14KK, with a 4–60 cM CASA/Rk intervalon the C57BL/6J background revealed that males, but not females,had decreased plasma plant sterol levels and intestinal cholesterolabsorption. In two subcongenic strains, 14PKK and 14DKK, with4–19.5 and 19.5–60 cM CASA/Rk intervals, respectively,both males and females had decreased plasma plant sterol levelsand decreased intestinal cholesterol absorption. Compatiblewith the decreased plasma plant sterol phenotype, 14PKK micehad increased biliary plant sterol excretion, whereas 14DKKmice did not. Therefore, gender-dependent interactions of genesat the 14PKK and 14DKK intervals are likely to underlie the14KK interval effect on plasma plant sterol levels and sterolabsorption from the intestine. These studies confirm the plasmaplant sterol locus on mouse chromosome 14 and provide evidencethat there are at least two sets of genes operating: one setaffecting 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