ZFIN ID: ZDB-PUB-130610-74
The zebrafish as a model to study polycystic liver disease
Tietz Bogert, P.S., Huang, B.Q., Gradilone, S.A., Masyuk, T.V., Moulder, G.L., Ekker, S.C., and Larusso, N.F.
Date: 2013
Source: Zebrafish   10(2): 211-217 (Journal)
Registered Authors: Ekker, Stephen C., Moulder, Gary
Keywords: none
MeSH Terms:
  • Animals
  • Antineoplastic Agents/administration & dosage
  • Antineoplastic Agents/therapeutic use
  • Cysts/drug therapy*
  • Cysts/etiology
  • Cysts/genetics*
  • Cysts/physiopathology
  • DNA Helicases/genetics
  • DNA Helicases/metabolism
  • Disease Models, Animal*
  • Gene Expression Regulation, Neoplastic*
  • Glucosidases/genetics
  • Glucosidases/metabolism
  • Humans
  • Intracellular Signaling Peptides and Proteins/genetics
  • Intracellular Signaling Peptides and Proteins/metabolism
  • Larva/metabolism
  • Liver Diseases/drug therapy*
  • Liver Diseases/etiology
  • Liver Diseases/genetics*
  • Liver Diseases/physiopathology
  • Morpholinos/administration & dosage
  • Morpholinos/metabolism
  • Phenylbutyrates/administration & dosage
  • Phenylbutyrates/therapeutic use
  • Polycystic Kidney, Autosomal Dominant/drug therapy*
  • Polycystic Kidney, Autosomal Dominant/etiology
  • Polycystic Kidney, Autosomal Dominant/genetics*
  • Polycystic Kidney, Autosomal Dominant/physiopathology
  • Somatostatin/administration & dosage
  • Somatostatin/analogs & derivatives
  • Somatostatin/therapeutic use
  • TRPP Cation Channels/genetics
  • TRPP Cation Channels/metabolism
  • Vitamin K 3/administration & dosage
  • Vitamin K 3/therapeutic use
  • Zebrafish*
PubMed: 23668934 Full text @ Zebrafish

In the polycystic liver diseases (PLD), genetic defects initiate the formation of cysts in the liver and kidney. In rodent models of PLD (i.e., the PCK rat and Pkd2WS25/ mouse), we have studied hepatorenal cystic disease and therapeutic approaches. In this study, we employed zebrafish injected with morpholinos against genes involved in the PLD, including sec63, prkcsh, and pkd1a. We calculated the liver cystic area, and based on our rodent studies, we exposed the embryos to pasireotide [1 μM] or vitamin K3 [100 μM] and assessed the endoplasmic reticulum (ER) in cholangiocytes in embryos treated with 4-phenylbutyrate (4-PBA). Our results show that (a) morpholinos against sec63, prkcsh, and pkd1a eliminate expression of the respective proteins; (b) phenotypic body changes included curved tail and the formation of hepatic cysts in zebrafish larvae; (c) exposure of embryos to pasireotide inhibited hepatic cystogenesis in the zebrafish models; and (d) exposure of embryos to 4-PBA resulted in the ER in cholangiocytes resolving from a curved to a smooth appearance. Our results suggest that the zebrafish model of PLD may provide a means to screen drugs that could inhibit hepatic cystogenesis.