ZFIN ID: ZDB-PUB-080714-8
Restoration of renal function in zebrafish models of ciliopathies
Tobin, J.L., and Beales, P.L.
Date: 2008
Source: Pediatric nephrology (Berlin, Germany)   23(11): 2095-2099 (Journal)
Registered Authors:
Keywords: Ciliopathy, Kidney cysts, Rapamycin, Roscovitine, Therapeutics
MeSH Terms:
  • Animals
  • Antineoplastic Agents/pharmacology*
  • Bardet-Biedl Syndrome/drug therapy
  • Bardet-Biedl Syndrome/genetics
  • Bardet-Biedl Syndrome/pathology
  • Cilia/pathology
  • Disease Models, Animal
  • Immunosuppressive Agents/pharmacology*
  • Kidney/physiology
  • Polycystic Kidney Diseases/drug therapy*
  • Polycystic Kidney Diseases/genetics
  • Polycystic Kidney Diseases/pathology
  • Purines/pharmacology*
  • Recovery of Function/drug effects
  • Sirolimus/pharmacology*
  • Zebrafish
PubMed: 18604564 Full text @ Pediatr. Nephrol.
The ciliopathies are a class of rare human genetic disease whose aetioligies lie in defective primary cilia. Typical ciliopathies include Bardet-Biedl syndrome (BBS), nephronophthisis (NPHP), Jeune, Joubert, oro-facial-digital (OFD1) and Meckel (MKS) syndromes. All ciliopathies have the common denominator of renal disease, often including tubular cysts. In this study, we have modelled a range of ciliopathies in zebrafish and shown in all cases that knocking down these genes causes cystic lesions in the kidney. We have identified two drugs, rapamycin and roscovitine, which ameliorate the renal phenotype, both morphologically and functionally. This is the first study in which zebrafish has been used to identify potential therapeutic modalities for ciliopathic renal disease, and the results pave the way for further investigations in mammalian models.