title: Restoration of renal function in zebrafish models of ciliopathies.
abstract: 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.
authors.affiliation: Molecular Medicine Unit, UCL Institute of Child Health, London, UK.
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Tobin
authors.forename: Philip L
authors.initials: PL
authors.lastname: Beales
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D020788:Bardet-Biedl Syndrome / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D002923:Cilia / Q000473:pathology; D004195:Disease Models, Animal; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007668:Kidney / Q000502:physiology; D007690:Polycystic Kidney Diseases / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D011687:Purines / Q000494:pharmacology*; D020127:Recovery of Function / Q000187:drug effects; D000077546:Roscovitine; D020123:Sirolimus / Q000494:pharmacology*; D015027:Zebrafish
chemical_list: D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; D011687:Purines; D000077546:Roscovitine; D020123:Sirolimus