A mouse model of GRIN2D developmental and epileptic encephalopathy recapitulates the human disease.
Brain : a journal of neurology April 25, 2025 Mor Yam, Jolan Nassir, Danielle Galber et al. 3 citations
A recurrent gain-of-function mutation in GRIN2D, which encodes an NMDA receptor subunit, causes developmental and epileptic encephalopathies. Mice carrying the orthologous mutation show premature death, spontaneous seizures, early motor deficits, and later cognitive impairment, closely mirroring the human disease. Electrophysiological recordings in cerebellar Purkinje neurons revealed developmental changes: reduced spontaneous firing in immature mice and augmented synaptic response to NMDA in older mice. Electrocorticography showed continuous abnormal brain activity with narrowband oscillations in theta, alpha, and beta bands, similar to a patient with the same variant. Low-dose ketamine had limited effect; higher doses caused seizures. Memantine and phenytoin produced small corrective effects on brain activity. These abnormal oscillations may serve as a biomarker for drug response.