A genetic screen in zebrafish identifies cilia genes as a principal cause of cystic kidney
Author:
Sun Zhaoxia1, Amsterdam Adam1, Pazour Gregory J.2, Cole Douglas G.3, Miller Mark S.3, Hopkins Nancy1
Affiliation:
1. MIT, Center for Cancer Research and Biology Department, Building E17 Room 340,77 Massachusetts Avenue, Cambridge, MA 02139, USA 2. Program in Molecular Medicine, University of Massachusetts Medical School, 373 Plantation Street, Worcester, MA 01605, USA 3. Department of Microbiology, Molecular Biology and Biochemistry (LSS142),University of Idaho, Moscow, ID 83844, USA
Abstract
Polycystic kidney disease (PKD) is a common human genetic illness. It is characterized by the formation of multiple kidney cysts that are thought to result from over-proliferation of epithelial cells. Zebrafish larvae can also develop kidney cysts. In an insertional mutagenesis screen in zebrafish, we identified 12 genes that can cause cysts in the glomerular-tubular region when mutated and we cloned 10 of these genes. Two of these genes, vhnf1(tcf2) and pkd2, are already associated with human cystic kidney diseases. Recently, defects in primary cilia have been linked to PKD. Strikingly, three out of the 10 genes cloned in this screen are homologues of Chlamydomonas genes that encode components of intraflagellar transport (IFT) particles involved in cilia formation. Mutation in a fourth blocks ciliary assembly by an unknown mechanism. These results provide compelling support for the connection between cilia and cystogenesis. Our results also suggest that lesions in genes involved in cilia formation and function are the predominant cause of cystic kidney disease, and that the genes identified here are excellent candidates for novel human PKD genes.
Publisher
The Company of Biologists
Subject
Developmental Biology,Molecular Biology
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