A mouse model of GRIN2D developmental and epileptic encephalopathy recapitulates the human disease.

ABSTRACT: Pathogenic variants in GRIN2D, encoding one of the subunits of the N-methyl-D-aspartate receptor (NMDAR), are associated with developmental and epileptic encephalopathies (DEEs). Unusual for de novo mutations, the recurrent, de novo, gain of function, missense mutation c.1999G>A (p.Val667Ile) was discovered in multiple patients. We characterized a mouse model carrying the orthologous Grin2d mutation, using behavioural paradigms, electrophysiological recordings in acute brain slices focusing mainly on the activity of Purkinje neurons in the cerebellum, and electrocorticography (ECoG) recordings monitoring brain activity and the response to several drugs. Grin2d mutant mice exhibit a range of phenotypes that closely mirror the human disease, including premature mortality, spontaneous seizure

SUBMITTER: Yam M 

PROVIDER: S-EPMC12782175 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature