Interacting QTLs for cholesterol gallstones and gallbladder mucin in AKR and SWR strains of mice.
We employed quantitative trait locus (QTL) mapping in a backcross between gallstone-susceptible SWR/J and gallstone-resistant AKR/J inbred mice to identify additional susceptibility loci for cholesterol gallstone formation. After 12 wk of feeding the mice a lithogenic diet, we phenotyped 330 backcross progeny for gallstones, gallbladder mucin accumulation, liver weight, and body weight. Marker-based regression analysis revealed significant single QTLs associated with gallstone formation on chromosome 9 and the liver weight/body weight ratio on chromosomes 5 and X. A search for gene pairs detected significant gene-gene interactions for mucin accumulation between loci on chromosomes 5 and 11 and suggestive gene-gene interactions linked to gallstone formation between the QTL on chromosome 9 and loci on chromosomes 6 and 15. These findings uncover new QTLs for cholesterol gallstones, reveal independent loci for mucin accumulation, and demonstrate the importance of considering gene-gene interactions in cholesterol cholelithiasis. According to standard nomenclature, the gallstone QTL on chromosome 9 is named Lith5.
Wittenburg
Henning
H
Jackson Laboratory, Bar Harbor, Maine 04609, USA.
Lammert
Frank
F
Wang
David Q-H
DQ
Churchill
Gary A
GA
Li
Renhua
R
Bouchard
Guylaine
G
Carey
Martin C
MC
Paigen
Beverly
B
D000818:Animals; D001835:Body Weight / Q000235:genetics; D002769:Cholelithiasis / Q000235:genetics*; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D004032:Diet; D005260:Female; D005704:Gallbladder / Q000737:chemistry* / Q000378:metabolism*; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D008099:Liver / Q000502:physiology; D008297:Male; D051379:Mice; D008806:Mice, Inbred AKR; D009077:Mucins / Q000235:genetics* / Q000378:metabolism; D009929:Organ Size / Q000235:genetics; D019655:Quantitative Trait, Heritable
D005819:Genetic Markers; D009077:Mucins