Cell
Volume 87, Issue 4, 15 November 1996, Pages 607-617
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Article
Absence Epilepsy in Tottering Mutant Mice Is Associated with Calcium Channel Defects

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Abstract

Mutations at the mouse tottering (tg) locus cause a delayed-onset, recessive neurological disorder resulting in ataxia, motor seizures, and behavioral absence seizures resembling petit mal epilepsy in humans. A more severe allele, leaner (tgla), also shows a slow, selective degeneration of cerebellar neurons. By positional cloning, we have identified an α1A voltage-sensitive calcium channel gene that is mutated in tg and tgla mice. The α1A gene is widely expressed in the central nervous system with prominent, uniform expression in the cerebellum. α1A expression does not mirror the localized pattern of cerebellar degeneration observed in tgla mice, providing evidence for regional differences in biological function of α1A channels. These studies define the first mutations in a mammalian central nervous system–specific voltage-sensitive calcium channel and identify the first gene involved in absence epilepsy.

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