Genetic ablation of NMDA receptor subunit NR3B in mouse reveals motoneuronal and nonmotoneuronal phenotypes.
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 approximately 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.
Niemann
Stephan
S
RIKEN-MIT Neuroscience Research Center, The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA. niste@mit.edu
Kanki
Hiroaki
H
Fukui
Yasuyuki
Y
Takao
Keizo
K
Fukaya
Masahiro
M
Hynynen
Meri N
MN
Churchill
Michael J
MJ
Shefner
Jeremy M
JM
Bronson
Roderick T
RT
Brown
Robert H
RH
Watanabe
Masahiko
M
Miyakawa
Tsuyoshi
T
Itohara
Shigeyoshi
S
Hayashi
Yasunori
Y
D000818:Animals; D001007:Anxiety / Q000523:psychology; D002452:Cell Count; D003213:Conditioning, Psychological / Q000502:physiology; D003463:Cues; D004644:Emotions / Q000502:physiology; D005239:Fear / Q000502:physiology; D005822:Genetic Vectors; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007398:Interpersonal Relations; D007858:Learning / Q000502:physiology; D018782:Maze Learning; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology; D009046:Motor Neurons / Q000502:physiology*; D018482:Muscle, Skeletal / Q000294:innervation / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D010641:Phenotype; D004856:Postural Balance / Q000502:physiology; D011597:Psychomotor Performance / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics* / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013126:Spinal Nerve Roots / Q000166:cytology
C501155:NR3B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate