Ataxia has been associated with abnormalities in neuronal differentiation and migration, which are regulated by Cyclin-dependent kinase 5 (Cdk5). The cerebellum of mice lacking Cdk5 or its activator, p35, resembles those of ataxic reeler and scrambler mice, suggesting that Cdk5 may contribute to ataxic pathology. As with other ataxic mice, the pogo/pogo mouse shows aberrant cerebellar tyrosine hydroxylase (TH) expression. Since Cdk5 phosphorylates and upregulates TH expression, we sought to analyze (i) Cdk5 activity in the pogo cerebellum, which exhibits abnormal TH expression, and (ii) TH expression in the cerebellum of p35−/− and p39−/− mice, which display reduced Cdk5 activity. Interestingly, we found that increased TH expression in the pogo cerebellum coincided with reduced Cdk5 activity. However, reduced Cdk5 activity in both p35−/− and p39−/− cerebellum did not correspond to defects in TH expression. Together, these suggest that abnormal TH expression in the cerebellum might be regulated by mechanisms other than Cdk5 activity.
Phosphorylation Purkinje cells Cerebellum Ataxia
This is a preview of subscription content, log in to check access
We thank Seung-Hyuk Chung for his excellent technical assistance. This project was supported by an operating grant from Canadian Institutes of Health Research to K-Y. Lee, an Alberta Heritage Foundation for Medical Research Senior Scholar.
Goldowitz D, Eisenman LM (1992) Genetic mutations affecting murine cerebellar structure and function. In: Driscoll P (ed) Genetically defined animal models of neurobehavioral dysfunction. Birkhauser, Boston, pp 66–88Google Scholar
Shelton SB, Johnson GV (2004) Cyclin-dependent kinase-5 in neurodegeneration. J Neurochem 88:1313–1326PubMedGoogle Scholar
Ohshima T, Ward JM, Huh CG et al (1996) Targeted disruption of the cyclin-dependent kinase 5 gene results in abnormal corticogenesis, neuronal pathology and perinatal death. Proc Natl Acad Sci USA 93:11173–11178. doi:10.1073/pnas.93.20.11173PubMedCrossRefGoogle Scholar
Napieralski JA, Eisenman LM (1996) Further evidence for a unique developmental compartment in the cerebellum of the meander tail mutant mouse as revealed by the quantitative analysis of Purkinje cells. J Comp Neurol 364:718–728. doi:10.1002/(SICI)1096-9861(19960122)364:4≤718::AID-CNE9≥3.0.CO;2-6PubMedCrossRefGoogle Scholar
Ko J, Humbert S, Bronson RT et al (2001) p35 and p39 are essential for cyclin-dependent kinase 5 function during neurodevelopment. J Neurosci 21:6758–6771PubMedGoogle Scholar