Adeno-Associated Virus-Mediated Gene Therapy in the Mashlool, Atp1a3^Mashl/+, Mouse Model of Alternating Hemiplegia of Childhood.

ABSTRACT: Alternating Hemiplegia of Childhood (AHC) is a devastating autosomal dominant disorder caused by ATP1A3 mutations, resulting in severe hemiplegia and dystonia spells, ataxia, debilitating disabilities, and premature death. Here, we determine the effects of delivering an extra copy of the normal gene in a mouse model carrying the most common mutation causing AHC in humans, the D801N mutation. We used an adeno-associated virus serotype 9 (AAV9) vector expressing the human ATP1A3 gene under the control of a human Synapsin promoter. We first demonstrated that intracerebroventricular (ICV) injection of this vector in wild-type mice on postnatal day 10 (P10) results in increases in ouabain-sensitive ATPase activity and in expression of reporter genes in targeted brain regions. We t

SUBMITTER: Hunanyan AS 

PROVIDER: S-EPMC8182483 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature