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Importance of the intracellular domain of NR2 subunits for NMDA receptor function in vivo.

TitleImportance of the intracellular domain of NR2 subunits for NMDA receptor function in vivo.
Publication TypeJournal Article
Year of Publication1998
AuthorsSprengel R, Suchanek B, Amico C, Brusa R, Burnashev N, Rozov A, Hvalby O, Jensen V, Paulsen O, Andersen P, Kim JJ, Thompson RF, Sun W, Webster LC, Grant SG, Eilers J, Konnerth A, Li J, McNamara JO, Seeburg PH
Date Published1998 Jan 23
KeywordsAmino Acid Sequence, Animals, Axons, Brain, Conditioning (Psychology), Evoked Potentials, Motor, Hippocampus, Kindling, Neurologic, Long-Term Potentiation, Male, Mice, Mice, Knockout, Molecular Sequence Data, Motor Skills, Nerve Tissue Proteins, Postural Balance, Receptors, N-Methyl-D-Aspartate, Sequence Deletion, Synaptic Transmission

NMDA receptors, a class of glutamate-gated cation channels with high Ca2+ conductance, mediate fast transmission and plasticity of central excitatory synapses. We show here that gene-targeted mice expressing NMDA receptors without the large intracellular C-terminal domain of any one of three NR2 subunits phenotypically resemble mice made deficient in that particular subunit. Mice expressing the NR2B subunit in a C-terminally truncated form (NR2B(deltaC/deltaC) mice) die perinatally. NR2A(deltaC/deltaC) mice are viable but exhibit impaired synaptic plasticity and contextual memory. These and NR2C(deltaC/deltaC) mice display deficits in motor coordination. C-terminal truncation of NR2 subunits does not interfere with the formation of gateable receptor channels that can be synaptically activated. Thus, the phenotypes of our mutants appear to reflect defective intracellular signaling.

Alternate JournalCell
PubMed ID9458051
Grant ListAF05142 / AF / ACF HHS / United States
AG0093 / AG / NIA NIH HHS / United States
IF32MN10521-01 / MN / OMHHE CDC HHS / United States
/ / Wellcome Trust / United Kingdom