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

Author(s)

Papale, Ligia A. ^{[1, 2]} ; Beyer, Barbara ^[3] ; Jones, Julie M. ^[4] ; Sharkey, Lisa M. ^[4] ; Tufik, Sergio ; Epstein, Michael ^[2] ; Letts, Verity A. ^[3] ; Meisler, Miriam H. ^[4] ; Frankel, Wayne N. ^[3] ; Escayg, Andrew ^[2]

Affiliation

^[1] Univ Fed Sao Paulo, Dept Psychobiol, Sao Paulo - Brazil

^[2] Emory Clin, Dept Human Genet, Atlanta, GA 30322 - USA

^[3] Jackson Lab, Bar Harbor, ME 04609 - USA

^[4] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 - USA

• Document type: Journal article
• Source: Human Molecular Genetics; v. 18, n. 9, p. 1633-1641, MAY 1 2009.
• Web of Science Citations: 70

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. (AU)

• FAPESP's process: 98/14303-3 - Center for Sleep Studies
• Grantee: Sergio Tufik
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC