SCN8A encephalopathy: Mechanisms and models

De novo mutations of the neuronal sodium channel SCN8A have been identified in approximately 2% of individuals with epileptic encephalopathy. These missense mutations alter the biophysical properties of sodium channel Nav1.6 in ways that lead to neuronal hyperexcitability. We generated two mouse models carrying patient mutations N1768D and R1872W to examine the effects on neuronal function in vivo. The conditional R1872W mutation is activated by...