出版社：American Society for Biochemistry and Molecular Biology
摘要：An intercross between C57BL/6J and CASA/Rk mice was used tostudy the genetics of biliary bile acid composition. In parentalstrains, male C57BL/6J mice had significantly higher cholicacid (CA; 14%) and lower ß-muricholic acid (ßMC;27%) than CASA/Rk mice, whereas females did not differ. However,quantitative trait locus analysis of F2 mice revealed no significantchromosome 9 loci in males but loci in females on chromosome9 for percentage CA (%CA) at 72 centimorgan (cM) [logarithmof the odds (LOD) 5.89] and %ßMC at 54 cM (LOD 4.09).Chromosome 9 congenic and subcongenic strains representing CASA/Rkintervals 38–73 cM (9KK) and 68–73 cM (9DKK) onthe C57BL/6J background were made. In 9KK and 9DKK males, %CAwas increased and %ßMC was unchanged, whereas in 9KKbut not 9DKK females, %CA was increased and %ßMC wasdecreased. Sterol 12-hydroxylase (Cyp8b1) channels bile acidprecursors into CA and maps at chromosome 9 (73 cM). However,there was no significant difference in Cyp8b1 mRNA or enzymaticactivity between parental mice, parental-congenic-subcongenicmice, or high-low biliary %CA F2 mice. In summary, two chromosome9 loci control sexually dimorphic effects on biliary bile acidcomposition: a distal (68–73 cM) major determinant inmales, and a more proximal (38–68 cM) major determinantin females. In this intercross, Cyp8b1, a strong candidate,does not appear to be responsible.Supplementary key words chenodeoxycholic acid • sterol 12-hydroxylase • cholic acid
Abbreviations: CA, cholic acid; CDCA, chenodeoxycholic acid; cM, centimorgan; CYP8B1, sterol 12-hydroxylase; LOD, logarithm of the odds; ßMC, ß-muricholic acid; QTL, quantitative trait locus
-hydroxylase (Cyp8b1) channels bile acid precursors into CA and maps at chromosome 9 (73 cM). However, there was no significant difference in Cyp8b1 mRNA or enzymatic activity between parental mice, parental-congenic-subcongenic mice, or high-low biliary %CA F2 mice. In summary, two chromosome 9 loci control sexually dimorphic effects on biliary bile acid composition: a distal (68–73 cM) major determinant in males, and a more proximal (38–68 cM) major determinant in females. In this intercross, Cyp8b1, a strong candidate, does not appear to be responsible.
Supplementary key words chenodeoxycholic acid • sterol 12
