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Zebrafish as a Model to Study Cholestatic Liver Diseases

  • Duc-Hung Pham
  • Chunyue YinEmail author
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1981)

Abstract

Cholestasis is a condition that impairs bile flow, resulting in retention of bile fluid in the liver. It may cause significant morbidity and mortality due to pruritus, malnutrition, and complications from portal hypertension secondary to biliary cirrhosis. The zebrafish (Danio rerio) has emerged as a valuable model organism for studying cholestasis that complements with the in vitro systems and rodent models. Its main advantages include conserved mechanisms of liver development and bile formation, rapid external development, ease of monitoring hepatobiliary morphology and function in live larvae, and accessibility to genetic and chemical manipulations. In this chapter, we provide an overview of the existing zebrafish models of cholestatic liver diseases. We discuss the strengths and limitations of using zebrafish to study cholestasis. We also provide step-by-step descriptions of the methodologies for analyzing cholestatic phenotypes in zebrafish.

Key words

Hepatocyte Cholangiocyte Bile duct Bile canaliculi Bile salt transporters BODIPY fluorescent fatty acid analog Fluorescent bile acid derivative Confocal microscopy Transmission electron microscopy 

Notes

Acknowledgments

We thank Drs. Steve Farber and Jessica Otis for sharing the original BODIPY protocol, Dr. Alan Hofmann for providing CGamF and C-NBD-L bile acid derivatives, Dr. Shinpei Kawaoka for advice on total bile salt measurement, and Dr. Kevin Bove and Ms. Georgianne Ciraolo for assistance with TEM. This work was supported by NIH grant R00AA020514 and American Gastroenterological Association AGA-Elsevier Pilot Research Award to C.Y., the Center for Pediatric Genomics at Cincinnati Children’s Hospital Medical Center, and NIH grant P30DK078392 to the Integrative Morphology Core of the Digestive Disease Research Core Center in Cincinnati.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Division of Gastroenterology, Hepatology and NutritionCincinnati Children’s Hospital Medical CenterCincinnatiUSA
  2. 2.Division of Developmental BiologyCincinnati Children’s Hospital Medical CenterCincinnatiUSA

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