title: A defect in a novel Nek-family kinase causes cystic kidney disease in the mouse and in zebrafish.
abstract: 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.
authors.affiliation: Genetics Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Shanming
authors.initials: S
authors.lastname: Liu
authors.forename: Weining
authors.initials: W
authors.lastname: Lu
authors.forename: Tomoko
authors.initials: T
authors.lastname: Obara
authors.forename: Shiei
authors.initials: S
authors.lastname: Kuida
authors.forename: Jennifer
authors.initials: J
authors.lastname: Lehoczky
authors.forename: Ken
authors.initials: K
authors.lastname: Dewar
authors.forename: Iain A
authors.initials: IA
authors.lastname: Drummond
authors.forename: David R
authors.initials: DR
authors.lastname: Beier
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002467:Cell Nucleus / Q000378:metabolism; D003001:Cloning, Molecular; D019992:Databases as Topic; D004195:Disease Models, Animal; D016678:Genome; D052177:Kidney Diseases, Cystic / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009154:Mutation; D000072379:NIMA-Related Kinases; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D020161:Physical Chromosome Mapping; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D015027:Zebrafish; D029961:Zebrafish Proteins
chemical_list: D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D029961:Zebrafish Proteins; D011494:Protein Kinases; C462119:NEK9 protein, human; D000072379:NIMA-Related Kinases; C499219:Nek8 protein, mouse; D017346:Protein Serine-Threonine Kinases; C499218:nek8 protein, zebrafish