Referenced in: none

Automatically associated channels: Nav1.6

Title: Heterozygous mutations of the voltage-gated sodium channel SCN8A are associated with spike-wave discharges and absence epilepsy in mice.

Authors: Ligia A Papale, Barbara Beyer, Julie M Jones, Lisa M Sharkey, Sergio Tufik, Michael Epstein, Verity A Letts, Miriam H Meisler, Wayne N Frankel, Andrew Escayg

Journal, date & volume: Hum. Mol. Genet., 2009 May 1 , 18, 1633-41

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/19254928

Abstract
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.