Knockout mouse - Its characteristics and application (1): NMDA receptor subunit knockout mouse

The N-methyl-D-aspartate (NMDA) type of glutamate receptors is thought to be essential in many central actions of neurotransmitter glutamate, including learning, memory, neurodevelopment and neurodegenerative disorders. Recent molecular cloning has revealed that the NMDA receptor has multiple subunits with distinct distribution, properties and regulation. This implies that NMDA receptors are different in molecular architecture and functional properties, depending on the brain region and developmental stage. To clarify the significance of the molecular diversity of NMDA receptors in vivo, a gene-targeting technique was applied to NMDA receptor subunit genes and several strains of mutant mice lacking targeted NMDA receptor subunit molecules were created. Using these NMDA receptor subunit knockout mice, various physiological, histological and behavioral analyses were performed. In this article, after briefly reviewing recent findings, we discuss the advantages and disadvantages of the NMDA receptor subunit knockout mouse as a tool for the studies of NMDA receptors and synaptic plasticity.