Quantitative trait loci mapping for cholesterol gallstones in AKR/J and C57L/J strains of mice

Quantitative trait locus (QTL) mapping was used to locate genes that determ ine the difference in cholesterol gallstone disease between the gallstone-s usceptible strain C57L/J and the gallstone-resistant strain AKR/J. Gallston e weight was determined in 231 male (AKR x C57L) F-1 x AKR backcross mice f ed a lithogenic diet containing 1% cholesterol, 0.5% cholic acid, and 15% b utterfat for 8 wk. Mice having no stones and mice having the largest stones were genotyped at similar to 20-cM intervals to find the loci determining cholesterol gallstone formation. The major locus, Lith1, mapped near D2Mit5 6 and was confirmed by constructing a congenic strain, AK.L-Lith1(s). Anoth er locus, Lith2, mapped near D19Mit58 and was also confirmed by constructin g a congenic strain AK.L-Lith2(s). Other suggestive, but not statistically significant, loci mapped to chromosomes 6, 7, 8, 10, and X. The identificat ion of these Lith genes will elucidate the pathophysiology of cholesterol g allstone formation.