Targeted disruption of the cyclin-dependent kinase 5 gene results in abnormal corticogenesis, neuronal pathology and perinatal death

Toshio Ohshima, Jerrold M. Ward, Chang Goo Huh, Glenn Longenecker, Veeranna, Harish C. Pant, Roscoe O. Brady, Lee J Martin, Ashok B. Kulkarni

Research output: Contribution to journalArticle

Abstract

Although cyclin-dependent kinase 5 (Cdk5) is closely related to other cyclin-dependent kinases, its kinase activity is detected only in the postmitotic neurons. Cdk5 expression and kinase activity are correlated with the extent of differentiation of neuronal cells in developing brain. Cdk5 purified from nervous tissue phosphorylates neuronal cytoskeletal proteins including neurofilament proteins and microtubule-associated protein tau in vitro. These findings indicate that Cdk5 may have unique functions in neuronal cells, especially in the regulation of phosphorylation of cytoskeletal molecules. We report here generation of CdkS(-/-) mice through gene targeting and their phenotypic analysis. Cdk5(-/-) mice exhibit unique lesions in the central nervous system associated with perinatal mortality. The brains of Cdk5(-/-) mice lack cortical laminar structure and cerebellar foliation. In addition, the large neurons in the brain stem and in the spinal cord show chromatolytic changes with accumulation of neurofilament immunoreactivity. These findings indicate that Cdk5 is an important molecule for brain development and neuronal differentiation and also suggest that Cdk5 may play critical roles in neuronal cytoskeleton structure and organization.

Original languageEnglish (US)
Pages (from-to)11173-11178
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume93
Issue number20
DOIs
StatePublished - Oct 1 1996

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Cyclin-Dependent Kinase 5
Pathology
Genes
Brain
Phosphotransferases
Neurofilament Proteins
Neurons
Nerve Tissue
Microtubule-Associated Proteins
Cytoskeletal Proteins
Gene Targeting
Intermediate Filaments
Cyclin-Dependent Kinases
Perinatal Mortality
Cytoskeleton
Brain Stem
Perinatal Death
Cell Differentiation
Spinal Cord
Central Nervous System

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Targeted disruption of the cyclin-dependent kinase 5 gene results in abnormal corticogenesis, neuronal pathology and perinatal death. / Ohshima, Toshio; Ward, Jerrold M.; Huh, Chang Goo; Longenecker, Glenn; Veeranna; Pant, Harish C.; Brady, Roscoe O.; Martin, Lee J; Kulkarni, Ashok B.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 93, No. 20, 01.10.1996, p. 11173-11178.

Research output: Contribution to journalArticle

Ohshima, Toshio ; Ward, Jerrold M. ; Huh, Chang Goo ; Longenecker, Glenn ; Veeranna ; Pant, Harish C. ; Brady, Roscoe O. ; Martin, Lee J ; Kulkarni, Ashok B. / Targeted disruption of the cyclin-dependent kinase 5 gene results in abnormal corticogenesis, neuronal pathology and perinatal death. In: Proceedings of the National Academy of Sciences of the United States of America. 1996 ; Vol. 93, No. 20. pp. 11173-11178.
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