The role of cyclin-dependent kinase 5 (Cdk5) in the plasticity of neuronal network : trials to make transgenic mice of Cdk5 and p35.

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1. Kinase activity of cyclin-dependent kinase 5 (Cdk5) was highest in 2-3 postnatal brains of rat and mouse.2. Expression levels of Cdk5 did not show significant change during development of brain, however, that of p35 showed a peak in 2-3 postnatal brains coinciding with Cdk5 activity.3. Cdk5/p35 activity in Alzheimer's brains was 20% higher than that in control brains. Especially, the activity in hippocampus in Alzheimer's brains increased by 30%, however, that in forebrain did not increase significantly.4. Immunohistochemical study elucidated that distribution of both Cdk5 and p35 was dominantly observed at the regions of paired helical tangles which is characteristic inAlzheimer's brains.5. Cdk activators, p35 and p39, and inhibitors, p21 and p27, were examined in Alzheimer's brains, and no significant change in expression levels was demonstrated.6. cDNAs of Cdk5 and p35 were transfected to PC12 cells using adeno virus, and high expression of both proteins were detected, However, the transfected cells showed no phenotipical changes. Transgenic mice which express high levels of both Cdk5 and p35 were tried to make, but the trials was unsuccessful. Knockout mice were also tried to establish, and made unsuccessfully.7. Our study elucidated that Cdk5/p35 in rat and mouse brains plays an important role in the developing brains during the period between later stage of embryo and 2-3 weeks postnatal.