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Updated: Oct 27, 2025
Extrahepatic Bile Duct and Gall Bladder Dissection in Nine-Day-Old Mouse Neonates
Published on: August 23, 2022
Early intrahepatic duct defects in a cystic fibrosis porcine model
Keyan Zarei1,2, David K Meyerholz3, David A Stoltz1,2,4,5
1Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA, USA.
Insights
Cystic fibrosis (CF) pigs show impaired bile duct fluid secretion and structural changes, contributing to reduced bile flow. This study investigates CFTR
Area of Science:
- Hepatobiliary science
- Gastroenterology
- Genetics
Background:
- Hepatobiliary disease is a serious complication in cystic fibrosis (CF).
- Previous studies in CF pigs revealed gallbladder issues, including mucus buildup and fluid secretion defects.
- The intrahepatic bile ducts in CF remain understudied.
Purpose of the Study:
- To investigate intrahepatic bile ducts in newborn CF pigs.
- To determine if CF pig cholangiocytes exhibit fluid secretion defects.
- To assess the presence of CFTR expression in porcine intrahepatic bile ducts.
Main Methods:
- Immunohistochemistry to detect CFTR expression in bile ducts.
- Serum marker analysis for hepatobiliary disease indicators.
- Quantitative histology to assess bile duct structure and mucus presence.
- Analysis of CF pig intrahepatic cholangiocyte organoids for fluid secretion.
Main Results:
- CF pig intrahepatic bile ducts lacked CFTR expression, unlike non-CF pigs.
- CF pigs exhibited smaller bile ducts with increased luminal mucus.
- CF pig cholangiocyte organoids were smaller and showed a lack of cAMP-mediated fluid secretion.
- Elevated direct bilirubin was observed, but other serum markers showed no significant disease signs.
Conclusions:
- Cholangiocyte fluid secretion is impaired in CF pigs.
- Defective fluid secretion contributes to structural bile duct changes and reduced biliary flow in CF.
- These findings highlight potential mechanisms for hepatobiliary complications in CF.
Abstract:
Hepatobiliary disease causes significant morbidity and mortality in people with cystic fibrosis (CF), yet this problem remains understudied. Previous studies in the newborn CF pig demonstrated decreased bile flow into the small intestine and a microgallbladder with increased luminal mucus and fluid secretion defects. In this study, we examined the intrahepatic bile ducts of the newborn CF pig. We assessed whether our findings from the gallbladder are present elsewhere in the porcine biliary tract and if CF pig cholangiocytes have fluid secretion defects. Immunohistochemistry demonstrated apical CFTR expression in non-CF pig intrahepatic bile ducts of a variety of sizes; CF pig intrahepatic bile ducts lacked CFTR expression. Assessment of serum markers did not reveal significant signs of hepatobiliary disease except for an elevation in direct bilirubin. Quantitative histology demonstrated that CF pigs had smaller bile ducts that more frequently contained luminal mucus. CF intrahepatic cholangiocyte organoids were smaller and lacked cAMP-mediated fluid secretion. Together these data suggest that cholangiocyte fluid secretion is decreased in the CF pig, contributing to structural changes in bile ducts and decreased biliary flow.
