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.
Liu
Shanming
S
Genetics Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Lu
Weining
W
Obara
Tomoko
T
Kuida
Shiei
S
Lehoczky
Jennifer
J
Dewar
Ken
K
Drummond
Iain A
IA
Beier
David R
DR
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
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