Strain background modifies phenotypes in the ATP8B1-deficient mouse

Sohela Shah, Ukina R. Sanford, Julie C. Vargas, Hongmei Xu, Annamiek Groen, Coen C. Paulusma, James P. Grenert, Ludmila Pawlikowska, Saunak Sen, Ronald P.J. Oude Elferink, Laura N. Bull

Research output: Contribution to journalArticle

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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. Methodology/Principal Findings: 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/ Significance: 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.

Original languageEnglish (US)
Article numbere8984
JournalPloS one
Volume5
Issue number2
DOIs
StatePublished - Feb 1 2010

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Liver
Phenotype
phenotype
Alkaline Phosphatase
mice
Cholates
129 Strain Mouse
Nutrition
Bilirubin
Animals
Cholesterol
alkaline phosphatase
Serum
animal models
Intrahepatic Cholestasis
liver
Hypercholesterolemia
bilirubin
liver diseases
Liver Diseases

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Shah, S., Sanford, U. R., Vargas, J. C., Xu, H., Groen, A., Paulusma, C. C., ... Bull, L. N. (2010). Strain background modifies phenotypes in the ATP8B1-deficient mouse. PloS one, 5(2), [e8984]. https://doi.org/10.1371/journal.pone.0008984

Strain background modifies phenotypes in the ATP8B1-deficient mouse. / Shah, Sohela; Sanford, Ukina R.; Vargas, Julie C.; Xu, Hongmei; Groen, Annamiek; Paulusma, Coen C.; Grenert, James P.; Pawlikowska, Ludmila; Sen, Saunak; Oude Elferink, Ronald P.J.; Bull, Laura N.

In: PloS one, Vol. 5, No. 2, e8984, 01.02.2010.

Research output: Contribution to journalArticle

Shah, S, Sanford, UR, Vargas, JC, Xu, H, Groen, A, Paulusma, CC, Grenert, JP, Pawlikowska, L, Sen, S, Oude Elferink, RPJ & Bull, LN 2010, 'Strain background modifies phenotypes in the ATP8B1-deficient mouse', PloS one, vol. 5, no. 2, e8984. https://doi.org/10.1371/journal.pone.0008984
Shah S, Sanford UR, Vargas JC, Xu H, Groen A, Paulusma CC et al. Strain background modifies phenotypes in the ATP8B1-deficient mouse. PloS one. 2010 Feb 1;5(2). e8984. https://doi.org/10.1371/journal.pone.0008984
Shah, Sohela ; Sanford, Ukina R. ; Vargas, Julie C. ; Xu, Hongmei ; Groen, Annamiek ; Paulusma, Coen C. ; Grenert, James P. ; Pawlikowska, Ludmila ; Sen, Saunak ; Oude Elferink, Ronald P.J. ; Bull, Laura N. / Strain background modifies phenotypes in the ATP8B1-deficient mouse. In: PloS one. 2010 ; Vol. 5, No. 2.
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