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