Restoration of renal function in zebrafish models of ciliopathies

The ciliopathiesare a class of rare human geneticdisease whose aetioligies lie in defective primary cilia. Typical ciliopathiesinclude Bardet–Biedl syndrome(BBS), nephronophthisis(NPHP), Jeune, Joubert, oro-facial-digital (OFD1) and Meckel (MKS) syndromes. All ciliopathieshave the common denominator of renal disease, often including tubular cysts. In this study, we have modelled a range of ciliopathiesin 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.