Novel mouse model of alternating hemiplegia of childhood exhibits prominent motor and seizure phenotypes.

ABSTRACT: Pathogenic variants in ATP1A3 encoding the neuronal Na/K-ATPase cause a spectrum of neurodevelopmental disorders including alternating hemiplegia of childhood (AHC). Three recurrent ATP1A3 variants are associated with approximately half of known AHC cases and mouse models of two of these variants (p.D801N, p.E815K) replicated key features of the human disorder, which include paroxysmal hemiplegia, dystonia and seizures. Epilepsy occurs in 40-50 % of individuals affected with AHC, but detailed investigations of seizure phenotypes were limited in the previously reported mouse models. Using gene editing, we generated a novel AHC mouse expressing the third most recurrent ATP1A3 variant (p.G947R) to model neurological phenotypes of the disorder. Heterozygous Atp1a3-G947R (Atp1a3^G947R

SUBMITTER: Hawkins NA 

PROVIDER: S-EPMC11808630 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature