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Tyrosine hydroxylase expression and Cdk5 kinase activity in ataxic cerebellum

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Abstract

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.

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Acknowledgments

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.

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Author notes

  1. Byung-Chul Lee

    Present address: Korea Advanced Institute of Science and Technology, DaeJeon, South Korea

  2. Young-Gil Jeong

    Present address: Department of Anatomy, College of Medicine, Konyang University, Nonsan, Chungnam, South Korea

Authors and Affiliations

  1. Department of Cell Biology and Anatomy, Southern Alberta Cancer Research Institute and Hotchkiss Brain Institute, The University of Calgary, Heritage Medical Research Building, 3330 Hospital Drive NW, Calgary, AB, Canada, T2N4N1

    K-John J. Cheung Jr., Jesusa L. Rosales, Byung-Chul Lee, Young-Gil Jeong & Ki-Young Lee

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  1. K-John J. Cheung Jr.
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Correspondence to Ki-Young Lee.

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Cheung, KJ.J., Rosales, J.L., Lee, BC. et al. Tyrosine hydroxylase expression and Cdk5 kinase activity in ataxic cerebellum. Mol Cell Biochem 318, 7–12 (2008). https://doi.org/10.1007/s11010-008-9850-1

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  • DOI: https://doi.org/10.1007/s11010-008-9850-1

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