Faculty Research 1990 - 1999
Absence epilepsy in tottering mutant mice is associated with calcium channel defects.
Document Type
Article
Publication Date
1996
Keywords
Animal, Apoptosis, Calcium-Channels: ge, cl, Cerebellum: pa, Chromosome-Mapping, Chromosomes-Yeast-Artificial, Cloning-Molecular, Crosses-Genetic, Epilepsy-Absence: et, ge, In-Situ-Hybridization, Ion-Channel-Gating: ge, Mice, Mice-Mutant-Strains, Molecular-Sequence-Data, Nerve-Tissue-Proteins: ge, cl, Polymerase-Chain-Reaction, Protein-Conformation, Sequence-Analysis-DNA, SUPPORT-NON-U-S-GOVT, SUPPORT-U-S-GOVT-P-H-S
First Page
607
Last Page
617
JAX Source
Cell 1996 Nov 15;87(4):607-17
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 (tg(la)), also shows a slow, selective degeneration of cerebellar neurons. By positional cloning, we have identified an alpha1A voltage-sensitive calcium channel gene that is mutated in tg and tg(la) mice. The alpha1A gene is widely expressed in the central nervous system with prominent, uniform expression in the cerebellum. alpha1A expression does not mirror the localized pattern of cerebellar degeneration observed in tg(la) mice, providing evidence for regional differences in biological function of alpha1A 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.
Recommended Citation
Fletcher CF,
Lutz CM,
O'Sullivan TN,
Shaughnessy JD,
Hawkes R,
Frankel WN,
Copeland NG,
Jenkins NA.
Absence epilepsy in tottering mutant mice is associated with calcium channel defects. Cell 1996 Nov 15;87(4):607-17