PUBLICATION
A Genetic Screen in Zebrafish Identifies Cilia Genes as a Principal Cause of Cystic Kidney Development
- Authors
- Sun, Z., Amsterdam, A., Pazour, G.J., Cole, D.G., Miller, M.S. and Hopkins, N.
- ID
- ZDB-PUB-040719-10
- Date
- 2004
- Source
- Development (Cambridge, England) 131(16): 4085-4093 (Journal)
- Registered Authors
- Amsterdam, Adam, Hopkins, Nancy, Sun, Zhaoxia
- Keywords
- PKD, Cilium, Zebrafish
- MeSH Terms
-
- Animals
- Cilia/genetics
- Cilia/metabolism
- Kidney/cytology
- Kidney/embryology
- Kidney/metabolism*
- Molecular Sequence Data
- Mutagenesis, Insertional
- Mutation
- Polycystic Kidney Diseases/embryology
- Polycystic Kidney Diseases/genetics*
- Polycystic Kidney Diseases/metabolism
- Zebrafish/genetics*
- Zebrafish/metabolism
- PubMed
- 15269167 Full text @ Development
Citation
Sun, Z., Amsterdam, A., Pazour, G.J., Cole, D.G., Miller, M.S. and Hopkins, N. (2004) A Genetic Screen in Zebrafish Identifies Cilia Genes as a Principal Cause of Cystic Kidney Development. Development (Cambridge, England). 131(16):4085-4093.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping