Heterozygous mutations of the voltage-gated sodium channel SCN8A are associated with spike-wave discharges and absence epilepsy in mice.
Base-Sequence, Disease-Models-Animal, Electrophysiology, Epilepsy-Absence, Heterozygote, Humans, Mice-Inbred-C3H, Mice-Inbred-C57BL, Mice-Transgenic, Molecular-Sequence-Data, Mutation, Mutation-Missense, Nerve-Tissue-Proteins, Phenotype, Sodium-Channels
Hum Mol Genet 2009 May; 18(9):1633-41.
In a chemical mutagenesis screen, we identified the novel Scn8a(8J) allele of the gene encoding the neuronal voltage-gated sodium channel Na(v)1.6. The missense mutation V929F in this allele alters an evolutionarily conserved residue in the pore loop of domain 2 of Na(v)1.6. Electroencephalography (EEG) revealed well-defined spike-wave discharges (SWD), the hallmark of absence epilepsy, in Scn8a(8J) heterozygotes and in heterozygotes for two classical Scn8a alleles, Scn8a(med) (null) and Scn8a(med-jo) (missense). Mouse strain background had a significant effect on SWD, with mutants on the C3HeB/FeJ strain showing a higher incidence than on C57BL/6J. The abnormal EEG patterns in heterozygous mutant mice and the influence of genetic background on SWD make SCN8A an attractive candidate gene for common human absence epilepsy, a genetically complex disorder.
Papale, L A.; Beyer, B; Jones, J M.; Sharkey, L M.; Tufik, S; Epstein, M; Letts, V A.; Meisler, M H.; Frankel, W N.; and Escayg, A, "Heterozygous mutations of the voltage-gated sodium channel SCN8A are associated with spike-wave discharges and absence epilepsy in mice." (2009). Faculty Research 2000 - 2009. 1977.