Title

Interacting QTLs for cholesterol gallstones and gallbladder mucin in AKR and SWR strains of mice.

Document Type

Article

Publication Date

2002

Keywords

Body-Weight, Cholelithiasis, Chromosome-Mapping, Crosses-Genetic, Diet, Female, Gallbladder, Genetic-Markers, Genetic-Predisposition-to-Disease, Liver, Male, Mice, Mice-Inbred-AKR, Mucins, Organ-Weight, Quantitative-Trait, SUPPORT-NON-U-S-GOVT, SUPPORT-U-S-GOVT-P-H-S

JAX Source

Physiol Genomics 2002 Feb; 8(1):67-77.

Abstract

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.