Early developmental deletion of forebrain Ank2 causes seizure-related phenotypes by reshaping the synaptic proteome.

ABSTRACT: Rare genetic variants in ANK2, which encodes ankyrin-B, are associated with neurodevelopmental disorders (NDDs); however, their pathogenesis is poorly understood. We find that mice with prenatal deletion in cortical excitatory neurons and oligodendrocytes (Ank2^-/-:Emx1-Cre), but not with adolescent deletion in forebrain excitatory neurons (Ank2^-/-:CaMKIIα-Cre), display severe spontaneous seizures, increased mortality, hyperactivity, and social deficits. Calcium imaging of cortical slices from Ank2^-/-:Emx1-Cre mice shows increased neuronal calcium event amplitude and frequency, along with network hyperexcitability and hypersynchrony. Quantitative proteomic analysis of cortical synaptic membranes reveals upregulation of dendritic spine plasticity-regulatory p

SUBMITTER: Yoon S 

PROVIDER: S-EPMC10566302 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature