Referenced in: none

Automatically associated channels: Cavα2δ2

Title: 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.

Authors: Jens Brodbeck, Anthony Davies, Jo-Maree Courtney, Alon Meir, Nuria Balaguero, Carles Cantí, Fraser J Moss, Karen M Page, Wendy S Pratt, Steven P Hunt, Jane Barclay, Michele Rees, Annette C Dolphin

Journal, date & volume: J. Biol. Chem., 2002 Mar 8 , 277, 7684-93

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/11756448

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.