Zebrafish as a Model to Study Cholestatic Liver Diseases.

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.