Liver-Specific β-Catenin Knockout Mice Have Bile Canalicular Abnormalities, Bile Secretory Defect, and Intrahepatic Cholestasis

Tzu Hsuan Yeh, Lindsay Krauland, Vijay Singh, Baobo Zou, Prathab Devaraj, Donna B. Stolz, Jonathan Franks, Satdarshan P.S. Monga, Eizaburo Sasatomi, Jaideep Behari

Research output: Contribution to journalArticlepeer-review

52 Scopus citations


Beta-catenin plays important roles in liver physiology and hepatocarcinogenesis. While studying the role of β-catenin in diet-induced steatohepatitis, we recently found that liver-specific β-catenin knockout (KO) mice exhibit intrahepatic cholestasis. This study was undertaken to further characterize the role of β-catenin in biliary physiology. KO mice and wild-type (WT) littermates were fed standard chow or a diet supplemented with 0.5% cholic acid for 2 weeks. Chow-fed KO mice had higher serum and hepatic total bile acid levels and lower bile flow rate than WT mice. Expression levels of bile acid biosynthetic genes were lower and levels of major bile acid exporters were similar, which therefore could not explain the KO phenotype. Despite loss of the tight junction protein claudin-2, KO mice had preserved functional integrity of tight junctions. KO mice had bile canalicular morphologic abnormalities as evidenced by staining for F-actin and zona occludens 1. Electron microscopy revealed dilated and tortuous bile canaliculi in KO livers along with decreased canalicular and sinusoidal microvilli. KO mice on a cholic acid diet had higher hepatic and serum bile acid levels, bile ductular reaction, increased pericellular fibrosis, and dilated, misshapen bile canaliculi. Compensatory changes in expression levels of several bile acid transporters and regulatory genes were found in KO livers. Conclusion: Liver-specific loss of β-catenin leads to defective bile canalicular morphology, bile secretory defect, and intrahepatic cholestasis. Thus, our results establish a critical role for β-catenin in biliary physiology.

Original languageEnglish (US)
Pages (from-to)1410-1419
Number of pages10
Issue number4
StatePublished - Oct 2010

ASJC Scopus subject areas

  • Hepatology


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