Heterozygous mutations of the voltage-gated sodium channel SCN8A are associated with spike-wave discharges and absence epilepsy in mice
Copyright policy )Heterozygous mutations of the voltage-gated sodium channel SCN8A are associated with spike-wave discharges and absence epilepsy in mice
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.
- UNIVERSIDADE DE SAO PAULO Brazil
- Universidade de São Paulo Brazil
- Universidade Federal de São Carlos Brazil
- Emory University United States
- University of Michigan–Flint United States
Heterozygote, 572, Molecular Sequence Data, Mutation, Missense, 610, Mice, Transgenic, Nerve Tissue Proteins, Base-Sequence, Nerve-Tissue-Proteins, Mice-Transgenic, Sodium Channels, 618, Mice, Animals, Humans, Mice-Inbred-C3H, Molecular-Sequence-Data, Sodium-Channels, Mice, Inbred C3H, Base Sequence, Mice-Inbred-C57BL, Articles, Electrophysiology, Mice, Inbred C57BL, Disease Models, Animal, Phenotype, Epilepsy, Absence, NAV1.6 Voltage-Gated Sodium Channel, Mutation, Disease-Models-Animal, Mutation-Missense, Epilepsy-Absence
Heterozygote, 572, Molecular Sequence Data, Mutation, Missense, 610, Mice, Transgenic, Nerve Tissue Proteins, Base-Sequence, Nerve-Tissue-Proteins, Mice-Transgenic, Sodium Channels, 618, Mice, Animals, Humans, Mice-Inbred-C3H, Molecular-Sequence-Data, Sodium-Channels, Mice, Inbred C3H, Base Sequence, Mice-Inbred-C57BL, Articles, Electrophysiology, Mice, Inbred C57BL, Disease Models, Animal, Phenotype, Epilepsy, Absence, NAV1.6 Voltage-Gated Sodium Channel, Mutation, Disease-Models-Animal, Mutation-Missense, Epilepsy-Absence
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