Perinatal abrogation of Cdk5 expression in brain results in neuronal migration defects

Motoyuki Hirasawa, Toshio Ohshima, Satoru Takahashi, Glenn Longenecker, Yasuyuki Honjo, Veeranna, Harish C. Pant, Katsuhiko Mikoshiba, Roscoe O. Brady, Ashok B. Kulkarni

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Cyclin-dependent kinase 5 (Cdk5) is essential for the proper development of the CNS, as is evident from the perinatal lethality of conventional Cdk5 knockout (Cdk5-/-) mice. Cdk5 is also implicated in numerous complex functions of the adult CNS such as synaptic transmission, synaptic plasticity, and neuronal signaling. To elucidate the molecular roles of Cdk5 in the adult CNS, we have abrogated neuronal expression of Cdk5 in perinatal mice by using a cre-loxP system. The Cdk5-loxP flanked mice were crossed with the cre-transgenic mice in which the cre expression is driven by the murine neurofilament-heavy chain promoter, resulting in generation of viable Cdk5 conditional knockout mice with the restricted deletion of the Cdk5 gene in specific neurons beginning around embryonic day 16.5. Twenty-five percent of the Cdk5 conditional knockout mice carrying the heterozygous cre allele had neuronal migration defects confined to brain areas where neuronal migration continues through the perinatal period. These results indicate that abrogation of Cdk5 expression in mature neurons results in a viable mouse model that offers further opportunities to investigate the molecular roles of Cdk5 in the adult CNS.

Original languageEnglish
Pages (from-to)6249-6254
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number16
DOIs
Publication statusPublished - 2004 Apr 20
Externally publishedYes

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Cyclin-Dependent Kinase 5
Brain
Knockout Mice
Neurons
Neuronal Plasticity
Intermediate Filaments
Synaptic Transmission
Transgenic Mice

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Perinatal abrogation of Cdk5 expression in brain results in neuronal migration defects. / Hirasawa, Motoyuki; Ohshima, Toshio; Takahashi, Satoru; Longenecker, Glenn; Honjo, Yasuyuki; Veeranna; Pant, Harish C.; Mikoshiba, Katsuhiko; Brady, Roscoe O.; Kulkarni, Ashok B.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 101, No. 16, 20.04.2004, p. 6249-6254.

Research output: Contribution to journalArticle

Hirasawa, M, Ohshima, T, Takahashi, S, Longenecker, G, Honjo, Y, Veeranna, Pant, HC, Mikoshiba, K, Brady, RO & Kulkarni, AB 2004, 'Perinatal abrogation of Cdk5 expression in brain results in neuronal migration defects', Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 16, pp. 6249-6254. https://doi.org/10.1073/pnas.0307322101
Hirasawa, Motoyuki ; Ohshima, Toshio ; Takahashi, Satoru ; Longenecker, Glenn ; Honjo, Yasuyuki ; Veeranna ; Pant, Harish C. ; Mikoshiba, Katsuhiko ; Brady, Roscoe O. ; Kulkarni, Ashok B. / Perinatal abrogation of Cdk5 expression in brain results in neuronal migration defects. In: Proceedings of the National Academy of Sciences of the United States of America. 2004 ; Vol. 101, No. 16. pp. 6249-6254.
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