Hepatic Canalicular Membrane Transport of Bile Salt in C57L/J and AKR/J Mice: Implications for Cholesterol Gallstone Formation

F. Hoda, R. M. Green*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

C57L/J (gallstone-susceptible) and AKR/J (gallstone-resistant) mice have been utilized for quantitative trait loci (QTL) analysis to identify the Lith 1 locus for cholelithiasis. Abcb11 encodes for the liver canalicular membrane bile salt export pump (BSEP), which maps to this QTL and is a candidate gene for Lith 1. We investigated the transmembrane transport of taurocholate in canalicular liver membrane vesicles isolated from these murine strains. Canalicular liver plasma membranes (cLPM) and RNA were isolated from C57L/J and AKR/J mice livers, and were utilized for Northern and Western blot analysis and functional 3H-taurocholate uptake studies. ATP-dependent 3H-taurocholate uptake was significantly higher in AKR/J, compared to C57L/J mice. Vmax was 127 vs. 42 pmol TC/mg/s in the murine strains, respectively, while Km was unchanged. In contrast, gene and protein expression of hepatic Abcb11 was increased three-fold in C57L/J, compared to AKR/J mice. Thus, Abcb11 bile salt transport activity per unit protein was reduced nine-fold in the C57L/J, compared to AKR/J mice. In contrast, canalicular membrane cholesterol:phospholipid content was also significantly higher in the C57L/J mice. We conclude that gallstone-susceptible C57L/J mice demonstrate increased gene and canalicular membrane expression of Abcb11, however, taurocholate transport is functionally diminished. The latter may be due to the increased cholesterol membrane content of the cLPM in C57L/J mice. These findings may be important for the pathogenesis of gallstone formation.

Original languageEnglish (US)
Pages (from-to)9-14
Number of pages6
JournalJournal of Membrane Biology
Volume196
Issue number1
DOIs
StatePublished - Nov 1 2003

Keywords

  • ABCB11
  • Bile salt export pump
  • Gallstone
  • Mice

ASJC Scopus subject areas

  • Biophysics
  • Physiology
  • Cell Biology

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