Current address: Epigenomics AG, Kleine Präsidentenstraße 1, 10178 Berlin, Federal Republic of Germany.
Genetic ablation of NMDA receptor subunit NR3B in mouse reveals motoneuronal and nonmotoneuronal phenotypes
Article first published online: 14 SEP 2007
European Journal of Neuroscience
Volume 26, Issue 6, pages 1407–1420, September 2007
How to Cite
Niemann, S., Kanki, H., Fukui, Y., Takao, K., Fukaya, M., Hynynen, M. N., Churchill, M. J., Shefner, J. M., Bronson, R. T., Brown, R. H., Watanabe, M., Miyakawa, T., Itohara, S. and Hayashi, Y. (2007), Genetic ablation of NMDA receptor subunit NR3B in mouse reveals motoneuronal and nonmotoneuronal phenotypes. European Journal of Neuroscience, 26: 1407–1420. doi: 10.1111/j.1460-9568.2007.05774.x
- Issue published online: 14 SEP 2007
- Article first published online: 14 SEP 2007
- Received 1 May 2007, revised 10 July 2007, accepted 19 July 2007
- excitatory synaptic transmission;
- gene targeting;
- motor neuron;
- mouse behaviour;
- NMDA type glutamate receptor subunit NR3B
NR3B is a modulatory subunit of the NMDA receptor, abundantly expressed in both cranial and spinal somatic motoneurons and at lower levels in other regions of the brain as well. Recently, we found the human NR3B gene (GRIN3B) to be highly genetically heterogeneous, and that ∼ 10% of the normal European-American population lacks NR3B due to homozygous occurrence of a null allele in the gene. Therefore, it is especially important to understand the phenotypic consequences of the genetic loss of NR3B in both humans and animal models. We here provide results of behavioral analysis of mice genetically lacking NR3B, which is an ideal animal model due to homogeneity in genetic and environmental background. The NR3B–/– mice are viable and fertile. Consistent with the expression of NR3B in somatic motoneurons, the NR3B–/– mice showed a moderate but significant impairment in motor learning or coordination, and decreased activity in their home cages. Remarkably, the NR3B–/– mice showed a highly increased social interaction with their familiar cage mates in their home cage but moderately increased anxiety-like behaviour and decreased social interaction in a novel environment, consistent with the inhibitory role of NR3B on the functions of NMDA receptors. This work is the first reporting of the functional significance of NR3B in vivo and may give insight into the contribution of genetic variability of NR3B in the phenotypic heterogeneity among human population.