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

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 l...

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Published in:Physiological genomics 2000-11, Vol.4 (1), p.59-65
Main Authors: PAIGEN, BEVERLY, SCHORK, NICHOLAS J, SVENSON, KAREN L, CHEAH, YIN-CHAI, MU, JIAN-LONG, LAMMERT, FRANK, WANG, DAVID Q.-H, BOUCHARD, GUYLAINE, CAREY, MARTIN C
Format: Article
Language:English
Subjects:
Animals
Cholelithiasis - genetics
Cholesterol - genetics
Cholesterol, Dietary - adverse effects
Chromosome Mapping - methods
Crosses, Genetic
Gallbladder - chemistry
Gallbladder - physiopathology
Genetic Markers
Genetic Predisposition to Disease - genetics
Male
Mice
Mice, Inbred AKR
Mice, Inbred C57BL
Organ Size - genetics
Quantitative Trait, Heritable
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Summary: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) F 1 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- Lith1 s . Another locus, Lith2 , mapped near D19Mit58 and was also confirmed by constructing a congenic strain AK.L- Lith2 s . 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
ISSN:1094-8341
1531-2267
DOI:10.1152/physiolgenomics.2000.4.1.59