Strain background modifies phenotypes in the ATP8B1-deficient mouse.

[benign recurrent intrahepatic cholestasis]

Mutations in ATP 8 B 1 (FIC 1 ) underlie cases of cholestatic disease , ranging from chronic and progressive (progressive familial intrahepatic cholestasis ) to intermittent (benign recurrent intrahepatic cholestasis ). The ATP 8 B 1 -deficient mouse serves as an animal model of human ATP 8 B 1 deficiency .We investigated the effect of genetic background on phenotypes of ATP 8 B 1 -deficient and wild-type mice , using C 5 7 Bl /6 (B 6 ), 129 , and (B 6 -129 ) F 1 strain backgrounds . B 6 background resulted in greater abnormalities in ATP 8 B 1 -deficient mice than did 129 and /or F 1 background . ATP 8 B 1 -deficient pups of B 6 background gained less weight . In adult ATP 8 B 1 -deficient mice at baseline , those of B 6 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 . ATP 8 B 1 -deficient phenotypes in mice of F 1 and 129 backgrounds are usually similar , suggesting that susceptibility to manifestations of ATP 8 B 1 deficiency may be recessive . We also detected differences in hepatobiliary phenotypes between wild-type mice of differing strains .Our results indicate that the ATP 8 B 1 -deficient mouse in a B 6 background may be a better model of human ATP 8 B 1 deficiency and highlight the importance of informed background strain selection for mouse models of liver disease .

Diseases
Validation

Diseases presenting "deficient mouse" symptom

benign recurrent intrahepatic cholestasis

lymphangioleiomyomatosis

werner syndrome

zellweger syndrome

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