Single locus mutations in mice expressing generalized spike-wave absence epilepsies.
Studies in mutant mice are beginning to reveal important general principles regarding the heredity of the spike-wave cortical synchronization trait. First, a defect at a single gene locus is sufficient to produce a generalized spike-wave seizure disorder. Second, the EEG pattern itself is genetically heterogeneous, and can arise from mutations in at least five independent loci. Third, the intervening cellular excitability mechanisms underlying the generation of spike-wave cortical discharges are not identical. Fourth, each of the mutant genes gives rise to syndromes that can differ in their seizure frequency, sensitivity to antiepileptic drugs, and severity of the associated neurological phenotype. Fifth, primary defects can be distinguished from secondary cellular alterations resulting from pathological neuronal synchronization. The patterns of these secondary changes vary according to the specific mutant allele, and may give rise to distinctive secondary phenotypes. The reproducibility of these defined genetic models may facilitate age-dependent antiepileptic drug discovery by defining novel targets for therapy at different developmental stages of the seizure disorder.
Noebels
J L
JL
Department of Neurology, Baylor College of Medicine, Houston, Texas 77030, USA.
D000200:Action Potentials; D000818:Animals; D002874:Chromosome Mapping; D003344:Cortical Synchronization; D004569:Electroencephalography; D004832:Epilepsy, Absence / Q000235:genetics*; D051379:Mice; D008818:Mice, Neurologic Mutants; D010641:Phenotype; D013577:Syndrome