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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

journal contribution
posted on 2023-05-17, 20:43 authored by Brodbeck, J, Davies, A, Jo-Maree CourtneyJo-Maree Courtney, Meir, A, Balaguero, N, Canti, C, Moss, FJ, Page, KM, Pratt, WS, Hunt, SP, Barclay, J, Rees, M, Dolphin, AC
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.

History

Publication title

Journal of Biological Chemistry

Volume

277

Issue

10

Pagination

7684-93

ISSN

0021-9258

Department/School

Tasmanian School of Medicine

Publisher

Amer Soc Biochemistry Molecular Biology Inc

Place of publication

9650 Rockville Pike, Bethesda, USA, Md, 20814-3996

Repository Status

  • Restricted

Socio-economic Objectives

Clinical health not elsewhere classified

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