A knock-in mouse model for GABRG2-related epileptic encephalopathy displays spontaneous generalized seizures and cognitive impairment.

ABSTRACT: De novo mutations in voltage- and ligand-gated ion channels have been associated with an increasing number of cases of developmental and epileptic encephalopathies (DEEs), which often fail to respond to classic antiseizure medications. A de novo mutation (c.C316G > A, p.A106T) in the human GABA type-A receptor γ2 subunit gene (GABRG2) has been recurrently identified in patients with DEE. In this study, we generated a knock-in mouse model replicating the human GABRG2(A106T) variation (Gabrg2^+/A105T in mouse). Gabrg2^+/A105T mice displayed early mortality, spontaneous seizures, and heightened seizure susceptibility. Behavioral analysis revealed phenotypes consistent with DEE, including impaired spatial learning and memory, as well as increased anxiety-like behavior. Redu

SUBMITTER: Shen D 

PROVIDER: S-EPMC12501280 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature