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Physiol. Genomics (December 18, 2001). doi:10.1152/physiolgenomics.00097.2001
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Articles in PresS, published online ahead of print December 18, 2001
Physiol Genomics, 10.1152/physiolgenomics.00097.2001
Submitted on October 11, 2001
Accepted on December 4, 2001

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

Henning Wittenburg1*, Frank Lammert2, David Q Wang2, Gary A Churchill3, Renhua Li3, Guylaine Bouchard4, Martin C Carey2, and Beverly Paigen3

1 The Jackson Laboratory, Bar Harbor, ME, USA; Medicine, Gastroenterology Division, Brigham and Women's Hospital, Harvard Digestive Diseases Center, Boston, MA, USA
2 Medicine, Gastroenterology Division, Brigham and Women's Hospital, Harvard Digestive Diseases Center, Boston, MA, USA; Gastroenterology Division, Brigham and Women's Hospital, Department of Medicine, Harvard Medical School, Boston, MA, USA
3 The Jackson Laboratory, Bar Harbor, ME, USA
4 Medicine, Gastroenterology Division, Brigham and Women's Hospital, Harvard Digestive Diseases Center, Boston, MA, USA

* To whom correspondence should be addressed. E-mail: hfw{at}jax.org.

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 weeks of feeding 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.




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