Grin2a Knockout mouse models

Grin2a is the mouse ortholog of human GRIN2A and encodes GluN2A, the glutamate-binding NMDA receptor subunit whose expression rises sharply after the second postnatal week and progressively replaces GluN2B at mature cortical and hippocampal synapses, conferring faster deactivation, higher open probability, and stronger sensitivity to extracellular zinc through its amino-terminal domain. Its shorter C-terminal tail binds PSD-95 and shifts downstream coupling away from the CaMKII-dominated signaling of GluN2B. Human variants populate the epilepsy-aphasia spectrum and developmental encephalopathies, and critically they split into loss-of-function and gain-of-function classes with opposite therapeutic implications, so patient knockins usually outperform simple deletion. Constitutive nulls are viable with impaired LTP and altered fear learning, making conditional alleles a tool for cell-type attribution rather than lethality rescue. Because Grin2b, Grin2c, and Grin2d can occupy the same tetramer position, quantify subunit-resolved kinetics and zinc sensitivity, and use humanized ligand-binding domains for subunit-selective modulator campaigns.

Whole body loss of Grin2a gives the clearest readout when the question is whether the gene is required at all. Follow up tissue work can still move to a conditional allele if lethality or compensation appears.