Figure 5.

Predominant role of excitatory neurons in SCN8A encephalopathy in the conditional R1872W mouse. Global pre-implantation activation of the mutant allele by EIIA-CRE results in seizure onset at 2 weeks of age followed rapidly by lethality. Activation of the mutant allele in excitatory forebrain neurons by Emx1 CRE also results in 100% penetrance of seizures and death, approximately 4 weeks later than the EIIA-CRE. In contrast, activation by the GAD2 CRE in inhibitory neurons had no detectable pathogenicity¹¹.