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The ducky mutation in Cacna2d2 results in altered Purkinje cell morphology and is associated with the expression of a truncated alpha 2 delta-2 protein with abnormal function

Citation

Brodbeck, J and Davies, A and Courtney, J and Meir, A and Balaguero, N and Canti, C and Moss, FJ and Page, KM and Pratt, WS and Hunt, SP and Barclay, J and Rees, M and Dolphin, AC, The ducky mutation in Cacna2d2 results in altered Purkinje cell morphology and is associated with the expression of a truncated alpha 2 delta-2 protein with abnormal function, Journal of Biological Chemistry, 277, (10) pp. 7684-93. ISSN 0021-9258 (2002) [Refereed Article]

DOI: doi:10.1074/jbc.M109404200

Abstract

The mouse mutant ducky, a model for absence epilepsy, is characterized by spike-wave seizures and cerebellar ataxia. A mutation in Cacna2d2, the gene encoding the alpha 2 delta-2 voltage-dependent calcium channel accessory subunit, has been found to underlie the ducky phenotype. The alpha 2 delta-2 mRNA is strongly expressed in cerebellar Purkinje cells. We show that du/du mice have abnormalities in their Purkinje cell dendritic tree. The mutation in alpha 2 delta-2 results in the introduction of a premature stop codon and predicts the expression of a truncated protein encoded by the first three exons of Cacna2d2, followed by 8 novel amino acids. We show that both mRNA and protein corresponding to this predicted transcript are expressed in du/du cerebellum and present in Purkinje cells. Whereas the alpha 2 delta-2 subunit increased the peak current density of the Ca(V)2.1/beta(4) channel combination when co-expressed in vitro, co-expression with the truncated mutant alpha 2 delta-2 protein reduced current density, indicating that it may contribute to the du phenotype.

Item Details

Item Type:Refereed Article
Research Division:Biological Sciences
Research Group:Biochemistry and Cell Biology
Research Field:Cell Neurochemistry
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Nervous System and Disorders
Author:Courtney, J (Dr Jo-Maree Courtney)
ID Code:87614
Year Published:2002
Web of Science® Times Cited:85
Deposited By:Medicine (Discipline)
Deposited On:2013-11-27
Last Modified:2013-11-27
Downloads:0

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