Novel E815K knock-in mouse model of alternating hemiplegia of childhood.

De novo mutations causing dysfunction of the ATP1A3 gene, which encodes the α3 subunit of Na/K-ATPase pump expressed in neurons, result in alternating hemiplegia of childhood (AHC). AHC manifests as paroxysmal episodes of hemiplegia, dystonia, behavioral abnormalities, and seizures. The first aim of this study was to characterize a novel knock-in mouse model (Atp1a3, Matoub, Matb) containing the E815K mutation of the Atp1a3 gene recognized as causing the most severe and second most common phenotype of AHC with increased morbidity and mortality as compared to other mutations.