Mice with genetically modified NMDA and AMPA receptors.
This manuscript summarizes mouse mutants for ionotropic glutamate receptors that were generated by different laboratories to analyze the function of the NMDA and AMPA receptors in the mouse. Thus, NMDA receptor mutant mice that were generated by the "knock-in" technology demonstrate that the NR1 and the NR2B subunits participate in the formation of NMDA receptors that are involved in vital functions like breathing and suckling of a newborn mouse. Mice that lack NR2A, -2C, and -2D subunits were described to be viable and have been used to study the role of NMDA receptors in adult mice. The depletion of the GluR-B subunit revealed an NMDA receptor-independent form of long-term potentiation (LTP). This AMPA receptor-mediated LTP at CA3/CA1 synapses was also observed in mice that carry an editing-deficient GluR-B allele even though these mice die prematurely after heavy epileptic seizures. In other mutants, the intracellular COOH-terminal domain of the NMDA receptor was truncated; and when compared to NMDA receptor "knock-out" mice, a functional knock-out of the NMDA receptor was observed. However, in the synapses of NR2AC/AC mutants, gatable NMDA receptors were synaptically activated, indicating that the knock-out phenotypes mediated by the COOH-terminally truncated NMDA receptors appear to reflect defective intracellular signaling.
Sprengel
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Department of Molecular Neurobiology, Max-Planck-Institute for Medical Research, Heidelberg, Germany. sprengel@mpimf-heidelberg.mpg.de
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D000818:Animals; D017353:Gene Deletion; D005786:Gene Expression Regulation; D017774:Long-Term Potentiation / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D017393:RNA Editing; D018091:Receptors, AMPA / Q000235:genetics*; D017470:Receptors, Glutamate / Q000235:genetics*; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics*; D013569:Synapses / Q000378:metabolism
D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate