• SCN1A is a gene encoding a voltage-gated sodium channel subunit, which is crucial for neuronal signaling. Mutation is SCN1A are associated with various epilepsy syndromes and these mutations primarily affect the inhibitory interneurons, leading to decreased inhibition and increased seizure susceptibility.
• The genome sequences between exon 3 and exon 27 were depleted in B-Scn1a KO mice(129S2), leading to the disruption of mouse Scn1a gene.
• Scn1a heterozygous knockout mice maintained on the 129S2/SvPasCrl background display no overt signs of disease or seizure phenotypes. By contrast, when these mice are crossed with wild-type C57BL/6J mice, the resulting hybrid offspring spontaneously develop epileptic phenotypes.

Gene targeting strategy for B-Scn1a KO mice(129S2). The genome sequences between exon 3 and exon 27 were depleted in B-Scn1a KO mice(129S2), leading to the disruption of mouse Scn1a gene.

Scn1a gene expression in wild-type 129S2/SvPasCrl mice and heterozygous B-Scn1a KO mice(129S2) by qPCR. Brains were collected from wild-type 129S2/SvPasCrl mice (+/+) (n=3, 4-week-old) and heterozygous B-Scn1a KO mice(129S2) (+/-) (n=3, 4-week-old). mRNA expression analysis was analyzed using qPCR. Each sample was assayed in triplicate replicates, with 40 ng total RNA loaded per well and relative expression in heterozygous mice was calculated by the 2^–ΔΔCt method. The data showed that mRNA expression level in heterozygous mice was approximately half of that in wild-type littermates, confirming the deletion of the mouse Scn1a in heterozygous B-Scn1a KO mice(129S2). Values are expressed as mean ± SEM.