International Mammalian Genome Society

The 15th International Mouse Genome Conference (2001)


POSTER 119 - INVESTIGATION OF THE CALCIUM CHANNEL DEFECT IN THE DUCKY MOUSE - A MODEL OF EPILEPSY AND ATAXIA

Dr. Michele Rees
University College London
Department of Paediatrics,
The Rayne Institute,
University Street,
London
WC1E 6JJ
UK

Co-Authors: 1) Barclay J, 2) Balaguero N, 3) Mione M, 4) Ackerman SL, 4) Letts VA, 2) Brodbeck J, 2) Canti C, 2) Meir A, 2) Page KM, 5) Kusumi K, 6) Perez-Reyes E, 5) Lander ES, 4) Frankel WN, 1) Gardiner RM, 2) Dolphin AC
Institutions: Departments of (1) Paediatrics, (2) Pharmacology and (3) Anatomy & Developmental Biology, University College London, (4) The Jackson Laboratory, (5) The Whitehead Institute, (6) University of Virginia.

The ducky (du) mouse is a spontaneous autosomal recessive mutant in which the homozygotes present with ataxia and spike wave discharges on cortical electroencephalogram detectable from around 15 days of age. These spike wave discharges coincide with periods of behavioural arrest similar to absence seizures seen in human idiopathic generalised epilepsy. Recently, we have demonstrated a mutation in the Cacna2d2 gene underlies the phenotype seen in the du/du mice and in a recently arising allele, du2J. The Cacna2d2 gene encodes the alpha2delta2 subunit of the voltage-dependent calcium channel complex. In brain, this subunit is expressed in a number of structures. It shows particularly high expression in the cerebellar Purkinje cells but is also expressed in the cerebral cortex, hippocampus, habenula, striatum and nucleus reticularis thalami. In Purkinje cells, the alpha2delta2 subnit contributes to the P-type calcium current and electro-physiological recordings from acutely dissociated Purkinje cells demonstrates a 35% reduction in the whole-cell calcium current in du/du compared with +/+ and +/du brain. Single channel recordings demonstrate that the calcium current through individual channels is unchanged across all three genotypes, therefore suggesting that the changes observed in whole cell current may be due to a reduction in the number of functional channels or in their open probability.


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