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

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.