title: Transgenic overexpression of Abcb11 enhances biliary bile salt outputs, but does not affect cholesterol cholelithogenesis in mice.
abstract: BACKGROUND
  Cholesterol gallstone disease is a complex genetic trait and induced by multiple but as yet unknown genes. A major Lith gene, Lith1 was first identified on chromosome 2 in gallstone-susceptible C57L mice compared with resistant AKR mice. Abcb11, encoding the canalicular bile salt export pump in the hepatocyte, co-localizes with the Lith1 QTL region and its hepatic expression is significantly higher in C57L mice than in AKR mice.
  
  
  METHODS
  To investigate whether Abcb11 influences cholesterol gallstone formation, we created an Abcb11 transgenic strain on the AKR genetic background and fed these mice with a lithogenic diet for 56 days.
  
  
  RESULTS
  We excluded functionally relevant polymorphisms of the Abcb11 gene and its promoter region between C57L and AKR mice. Overexpression of Abcb11 significantly promoted biliary bile salt secretion and increased circulating bile salt pool size and bile salt-dependent bile flow rate. However, biliary cholesterol and phospholipid secretion, as well as gallbladder size and contractility were comparable in transgenic and wild-type mice. At 56 days on the lithogenic diet, cholesterol saturation indexes of gallbladder biles and gallstone prevalence rates were essentially similar in these two groups of mice.
  
  
  CONCLUSIONS
  Overexpression of Abcb11 augments biliary bile salt secretion, but does not affect cholelithogenesis in mice.
authors.affiliation: Beth Israel Deaconess Medical Center, Harvard Medical School and Harvard Digestive Diseases Center, Boston, MA 02215, USA.
authors.forename: Helen H
authors.initials: HH
authors.lastname: Wang
authors.forename: Frank
authors.initials: F
authors.lastname: Lammert
authors.forename: Anne
authors.initials: A
authors.lastname: Schmitz
authors.forename: David Q-H
authors.initials: DQ
authors.lastname: Wang
mesh_terms: D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism*; D002769:Cholelithiasis / Q000235:genetics / Q000378:metabolism*; D002791:Cholesterol, Dietary / Q000494:pharmacology*; D005704:Gallbladder / Q000503:physiopathology; D042882:Gallstones / Q000235:genetics*; D050356:Lipid Metabolism; D051379:Mice; D008822:Mice, Transgenic / Q000378:metabolism; D011401:Promoter Regions, Genetic; D017422:Sequence Analysis, DNA
chemical_list: C093491:ABCB11 protein, human; D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters; D001647:Bile Acids and Salts; D002791:Cholesterol, Dietary
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