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Polycystic kidney rat is a novel animal model of Caroli's disease associated with congenital hepatic fibrosis.
American Journal of Pathology 2001 May
Caroli's disease (congenital intrahepatic biliary dilatation) associated with congenital hepatic fibrosis is an autosomal recessive polycystic kidney disease. Recently, the polycystic kidney (PCK) rat, a spontaneous mutant derived from a colony of CRJ:CD rats with polycystic lesions in the liver and an autosomal recessive mode of inheritance, was reported. In the present study, the pathology of the hepatobiliary system and the biliary cell-kinetics were evaluated in fetuses (day 18 to 21 of gestation) and neonates and adults (1 day to 4 months after delivery) of PCK rats. CRJ:CD rats were used as a control. Multiple segmental and saccular dilatations of intrahepatic bile ducts were first observed in fetuses at 19 days of gestation. The dilatation spread throughout the liver and the degree of dilatation increased with aging. Gross and histological features characterizing ductal plate malformation were common in the intrahepatic bile ducts. Overgrowth of portal connective tissue was evident and progressive after delivery. These features were very similar to those of Caroli's disease with congenital hepatic fibrosis. Proliferative activity in the biliary epithelial cells was greater in PCK rats than controls during the development. In contrast, the biliary epithelial apoptosis was less extensive in PCK rats than the controls until 1 week after delivery, but greater after 3 weeks, suggesting that the remodeling defect in immature bile ducts associated with the imbalance of cell kinetics plays a role in the occurrence of intrahepatic biliary anomalies in PCK rats. The PCK rat could be a useful and promising animal model of Caroli's disease with congenital hepatic fibrosis.
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