title: Perinatal abrogation of Cdk5 expression in brain results in neuronal migration defects.
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.
authors.affiliation: Functional Genomics Unit, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Motoyuki
authors.initials: M
authors.lastname: Hirasawa
authors.forename: Toshio
authors.initials: T
authors.lastname: Ohshima
authors.forename: Satoru
authors.initials: S
authors.lastname: Takahashi
authors.forename: Glenn
authors.initials: G
authors.lastname: Longenecker
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Honjo
authors.lastname: Veeranna
authors.forename: Harish C
authors.initials: HC
authors.lastname: Pant
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Mikoshiba
authors.forename: Roscoe O
authors.initials: RO
authors.lastname: Brady
authors.forename: Ashok B
authors.initials: AB
authors.lastname: Kulkarni
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D001921:Brain / Q000166:cytology / Q000201:enzymology*; D002465:Cell Movement / Q000502:physiology*; D051360:Cyclin-Dependent Kinase 5; D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology / Q000201:enzymology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D051360:Cyclin-Dependent Kinase 5; C495906:Cdk5 protein, mouse; D018844:Cyclin-Dependent Kinases