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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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COS Cells
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Cell Nucleus / metabolism
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Cloning, Molecular
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Databases as Topic
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Disease Models, Animal
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Genome
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Kidney Diseases, Cystic / genetics*
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Mice
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Mice, Inbred C57BL
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Models, Genetic
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Molecular Sequence Data
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Mutation
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NIMA-Related Kinases
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Oligonucleotides, Antisense / pharmacology
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Physical Chromosome Mapping
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Protein Kinases*
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Protein Serine-Threonine Kinases / genetics*
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Protein Serine-Threonine Kinases / physiology*
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RNA, Messenger / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Time Factors
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Zebrafish
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Zebrafish Proteins
Substances
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Oligonucleotides, Antisense
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RNA, Messenger
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Zebrafish Proteins
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Protein Kinases
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NEK9 protein, human
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NIMA-Related Kinases
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Nek8 protein, mouse
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Protein Serine-Threonine Kinases
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nek8 protein, zebrafish