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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 |
| Objective Field: | Clinical health not elsewhere classified |
| UTAS Author: | Courtney, J (Dr Jo-Maree Courtney) |
| ID Code: | 87614 |
| Year Published: | 2002 |
| Web of Science® Times Cited: | 108 |
| Deposited By: | Medicine |
| Deposited On: | 2013-11-27 |
| Last Modified: | 2013-11-27 |
| Downloads: | 0 |
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