Arx expansion mutation perturbs cortical development by augmenting apoptosis without activating innate immunity in a mouse model of X-linked infantile spasms syndrome.

ABSTRACT: X-linked infantile spasms syndrome (ISSX) is a clinically devastating developmental epileptic encephalopathy with life-long impact. Arx^(GCG)10+7 , a mouse model of the most common triplet-repeat expansion mutation of ARX, exhibits neonatal spasms, electrographic phenotypes and abnormal migration of GABAergic interneuron subtypes. Neonatal presymptomatic treatment with 17β-estradiol (E2) in Arx^(GCG)10+7 reduces spasms and modifies progression of epilepsy. Cortical pathology during this period, a crucial point for clinical intervention in ISSX, has largely been unexplored, and the pathogenic cellular defects that are targeted by early interventions are unknown. In the first postnatal week, we identified a transient wave of elevated apoptosis in A

SUBMITTER: Siehr MS 

PROVIDER: S-EPMC7132796 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature