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1 The Jackson Laboratory, Bar Harbor, Maine 04609
2 Department of Medicine, Harvard Medical School, Gastroenterology Division, Brigham and Women’s Hospital and Harvard Digestive Diseases Center, Boston, Massachusetts 02115
3 Case Western Reserve University, Cleveland, Ohio 44109
Quantitative trait locus (QTL) mapping was used to locate genes that determine the difference in cholesterol gallstone disease between the gallstone-susceptible strain C57L/J and the gallstone-resistant strain AKR/J. Gallstone weight was determined in 231 male (AKR x C57L) F1 x AKR backcross mice fed a lithogenic diet containing 1% cholesterol, 0.5% cholic acid, and 15% butterfat for 8 wk. Mice having no stones and mice having the largest stones were genotyped at 
20-cM intervals to find the loci determining cholesterol gallstone formation. The major locus, Lith1, mapped near D2Mit56 and was confirmed by constructing a congenic strain, AK.L-Lith1s. Another locus, Lith2, mapped near D19Mit58 and was also confirmed by constructing a congenic strain AK.L-Lith2s. Other suggestive, but not statistically significant, loci mapped to chromosomes 6, 7, 8, 10, and X. The identification of these Lith genes will elucidate the pathophysiology of cholesterol gallstone formation.
congenic; recombinant inbred strain; gallbladder; genetics; Abcc2; Abcb11
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