Perinatal Abrogation of Cdk5 Expression in Brain Results in Neuronal Migration Defects

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, an...

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Published in:Proceedings of the National Academy of Sciences - PNAS 2004-04, Vol.101 (16), p.6249-6254
Main Authors: Hirasawa, Motoyuki, Ohshima, Toshio, Takahashi, Satoru, Longenecker, Glenn, Honjo, Yasuyuki, Veeranna, Pant, Harish C., Mikoshiba, Katsuhiko, Brady, Roscoe O., Kulkarni, Ashok B.
Format: Article
Language:English
Subjects:
Alleles
Animals
Antibodies
Biological Sciences
Blotting, Northern
Brain
Brain - cytology
Brain - enzymology
Cell Movement - physiology
Central nervous system
Cerebellum
Cyclin-Dependent Kinase 5
Cyclin-Dependent Kinases - genetics
Cyclin-Dependent Kinases - physiology
Gene expression
Messenger RNA
Mice
Mice, Knockout
Neuroglia
Neurology
Neurons
Neurons - cytology
Neurons - enzymology
Purkinje cells
Reverse Transcriptase Polymerase Chain Reaction
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0307322101