title: Strain background modifies phenotypes in the ATP8B1-deficient mouse.
abstract: BACKGROUND
  Mutations in ATP8B1 (FIC1) underlie cases of cholestatic disease, ranging from chronic and progressive (progressive familial intrahepatic cholestasis) to intermittent (benign recurrent intrahepatic cholestasis). The ATP8B1-deficient mouse serves as an animal model of human ATP8B1 deficiency.
  
  
  RESULTS
  We investigated the effect of genetic background on phenotypes of ATP8B1-deficient and wild-type mice, using C57Bl/6 (B6), 129, and (B6-129) F1 strain backgrounds. B6 background resulted in greater abnormalities in ATP8B1-deficient mice than did 129 and/or F1 background. ATP8B1-deficient pups of B6 background gained less weight. In adult ATP8B1-deficient mice at baseline, those of B6 background had lower serum cholesterol levels, higher serum alkaline phosphatase levels, and larger livers. After challenge with cholate-supplemented diet, these mice exhibited higher serum alkaline phosphatase and bilirubin levels, greater weight loss and larger livers. ATP8B1-deficient phenotypes in mice of F1 and 129 backgrounds are usually similar, suggesting that susceptibility to manifestations of ATP8B1 deficiency may be recessive. We also detected differences in hepatobiliary phenotypes between wild-type mice of differing strains.
  
  
  CONCLUSIONS
  Our results indicate that the ATP8B1-deficient mouse in a B6 background may be a better model of human ATP8B1 deficiency and highlight the importance of informed background strain selection for mouse models of liver disease.
authors.affiliation: UCSF Liver Center, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Sohela
authors.initials: S
authors.lastname: Shah
authors.forename: Ukina R
authors.initials: UR
authors.lastname: Sanford
authors.forename: Julie C
authors.initials: JC
authors.lastname: Vargas
authors.forename: Hongmei
authors.initials: H
authors.lastname: Xu
authors.forename: Annamiek
authors.initials: A
authors.lastname: Groen
authors.forename: Coen C
authors.initials: CC
authors.lastname: Paulusma
authors.forename: James P
authors.initials: JP
authors.lastname: Grenert
authors.forename: Ludmila
authors.initials: L
authors.lastname: Pawlikowska
authors.forename: Saunak
authors.initials: S
authors.lastname: Sen
authors.forename: Ronald P J Oude
authors.initials: RP
authors.lastname: Elferink
authors.forename: Laura N
authors.initials: LN
authors.lastname: Bull
mesh_terms: D000251:Adenosine Triphosphatases / Q000172:deficiency* / Q000235:genetics; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D000831:Animals, Newborn; D001663:Bilirubin / Q000097:blood; D020355:Cholates / Q000008:administration & dosage; D002780:Cholestasis, Intrahepatic / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D002784:Cholesterol / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D010641:Phenotype; D049294:Phospholipid Transfer Proteins; D013045:Species Specificity; D016019:Survival Analysis; D015430:Weight Gain / Q000187:drug effects
chemical_list: D020355:Cholates; D049294:Phospholipid Transfer Proteins; D002784:Cholesterol; D000469:Alkaline Phosphatase; D000251:Adenosine Triphosphatases; C491742:Atp8b1 protein, mouse; D001663:Bilirubin