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

Henning Wittenburg, Frank Lammert, David Q.H. Wang, Gary A. Churchill, Renhua Li, Guylaine Bouchard, Martin C. Carey, Beverly Paigen

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)67-77
Number of pages11
JournalPhysiological genomics
Volume2002
Issue number8
DOIs
StatePublished - Apr 2002

Keywords

  • Gene-gene interaction
  • Genetics
  • Inbred mouse strains
  • Obesity

ASJC Scopus subject areas

  • Physiology
  • Genetics

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