Fig. 1

Genomic context of SCN1A gene and Scn1a 1b deletion mouse model generation. a Human (hg19) SCN1A locus showing signal for histone PTMs and ATAC-seq for neuronal and non-neuronal cells derived from dorsolateral PFC. b Activity of human 1b region in luciferase assay with minimal promoter in HEK293 (****P < 0.0001) and SK-N-SH cells (****P < 0.0001) shown as mean ± SEM. c Transcriptional activation of SCN1A using gRNAs targeting 1b co-transfected with dCas9-p300 in HEK293 cells increases SCN1A expression (*P = 0.047) when compared to empty vector (EV) as measured by qPCR and normalized to non-transfected control, shown as mean ± SEM. d Mouse (mm10) Scn1a locus showing signal for histone PTMs and ATAC-seq for neuronal cell types. e Mouse Scn1a 1b locus showing guideRNA sequence targets for Cas9-directed deletion of mouse 1b removal of entire 3063 bp conserved region and sequence trace validating deleted region. f Survival curve for offspring from 1b^+/− by 1b^+/− breeding pairs. Data is from 13 litters that dropped from 3 generations of pairings combined. 1b^+/− and 1b^+/+ log-rank p value = 0.5455; 1b^+/+ versus 1b^−/− log-rank p value < 0.0001. For panels a and d, see text for data sources