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.

Genetic localization of interacting modifiers affecting severity in a murine model of polycystic kidney disease.

Genetic analysis of mouse disease models provides a means to investigate how modifying loci cause variation in phenotypic expression. We have shown that polycystic kidney disease (PKD) progression in the juvenile cystic kidney (jck) mutation can be influenced by an epistatic interaction between alleles of different strain backgrounds and we localized one of these loci to chromosome 1. Using a chromosome 1 congenic strain, we improved the genetic analysis and mapped the interacting locus to proximal chromosome 4, with a highly significant lod association of 5.