Heterozygous mutations of the voltage-gated sodium channel SCN8A are associated with spike-wave discharges and absence epilepsy in mice
Papale, Ligia Assumpção [UNIFESP]
Jones, Julie M.
Sharkey, Lisa M.
Tufik, Sergio [UNIFESP]
Letts, Verity A.
Meisler, Miriam H.
Frankel, Wayne N.
Is part ofHuman Molecular Genetics
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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.
CitationHuman Molecular Genetics. Oxford: Oxford Univ Press, v. 18, n. 9, p. 1633-1641, 2009.
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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