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

Development. 2002 Dec;129(24):5839-46. doi: 10.1242/dev.00173.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • COS Cells
  • Cell Nucleus / metabolism
  • Cloning, Molecular
  • Databases as Topic
  • Disease Models, Animal
  • Genome
  • Kidney Diseases, Cystic / genetics*
  • Mice
  • Mice, Inbred C57BL
  • Models, Genetic
  • Molecular Sequence Data
  • Mutation
  • NIMA-Related Kinases
  • Oligonucleotides, Antisense / pharmacology
  • Physical Chromosome Mapping
  • Protein Kinases*
  • Protein Serine-Threonine Kinases / genetics*
  • Protein Serine-Threonine Kinases / physiology*
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Time Factors
  • Zebrafish
  • Zebrafish Proteins


  • Oligonucleotides, Antisense
  • RNA, Messenger
  • Zebrafish Proteins
  • Protein Kinases
  • NEK9 protein, human
  • NIMA-Related Kinases
  • Nek8 protein, mouse
  • Protein Serine-Threonine Kinases
  • nek8 protein, zebrafish