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doi: 10.1242/10.1242/dev.00173

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A defect in a novel Nek-family kinase causes cystic kidney disease in the mouse and in zebrafish

¹ Genetics Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
² Renal Unit, Massachusetts General Hospital, Boston, MA, USA
³ Whitehead Institute for Biomedical Research/MIT Center for Genome Research, Cambridge, MA, USA

^* Author for correspondence (e-mail: beier{at}rascal.med.harvard.edu

Accepted 23 September 2002

The murine autosomal recessive juvenile cystic kidney (jck) mutation results in polycystic kidney disease. We have identified in jck mice a mutation in Nek8, a novel and highly conserved member of the Nek kinase family. In vitro expression of mutated Nek8 results in enlarged, multinucleated cells with an abnormal actin cytoskeleton. To confirm that a defect in the Nek8 gene can cause cystic disease, we performed a cross-species analysis: injection of zebrafish embryos with a morpholino anti-sense oligonucleotide corresponding to the ortholog of Nek8 resulted in the formation of pronephric cysts. These results demonstrate that comparative analysis of gene function in different model systems represents a powerful means to annotate gene function.

Key words: PKD, mouse models, zebrafish, Nek kinase

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