Genetic ablation of NMDA receptor subunit NR3B in mouse reveals motoneuronal and nonmotoneuronal phenotypes

Stephan Niemann, Hiroaki Kanki, Yasuyuki Fukui, Keizo Takao, Masahiro Fukaya, Meri N. Hynynen, Michael J. Churchill, Jeremy M. Shefner, Roderick T. Bronson, Robert H. Brown, Masahiko Watanabe, Tsuyoshi Miyakawa, Shigeyoshi Itohara, Yasunori Hayashi

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1407-1420
Number of pages14
JournalEuropean Journal of Neuroscience
Volume26
Issue number6
DOIs
Publication statusPublished - 01-09-2007

Fingerprint

Phenotype
Motor Neurons
Interpersonal Relations
N-Methyl-D-Aspartate Receptors
Animal Models
Population
Genes
Anxiety
Alleles
Learning
NR3B NMDA receptor
Brain
Genetic Background

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Niemann, Stephan ; Kanki, Hiroaki ; Fukui, Yasuyuki ; Takao, Keizo ; Fukaya, Masahiro ; Hynynen, Meri N. ; Churchill, Michael J. ; Shefner, Jeremy M. ; Bronson, Roderick T. ; Brown, Robert H. ; Watanabe, Masahiko ; Miyakawa, Tsuyoshi ; Itohara, Shigeyoshi ; Hayashi, Yasunori. / Genetic ablation of NMDA receptor subunit NR3B in mouse reveals motoneuronal and nonmotoneuronal phenotypes. In: European Journal of Neuroscience. 2007 ; Vol. 26, No. 6. pp. 1407-1420.
@article{579d46a4889e4e2ea9534ee39485d549,
title = "Genetic ablation of NMDA receptor subunit NR3B in mouse reveals motoneuronal and nonmotoneuronal phenotypes",
abstract = "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.",
author = "Stephan Niemann and Hiroaki Kanki and Yasuyuki Fukui and Keizo Takao and Masahiro Fukaya and Hynynen, {Meri N.} and Churchill, {Michael J.} and Shefner, {Jeremy M.} and Bronson, {Roderick T.} and Brown, {Robert H.} and Masahiko Watanabe and Tsuyoshi Miyakawa and Shigeyoshi Itohara and Yasunori Hayashi",
year = "2007",
month = "9",
day = "1",
doi = "10.1111/j.1460-9568.2007.05774.x",
language = "English",
volume = "26",
pages = "1407--1420",
journal = "European Journal of Neuroscience",
issn = "0953-816X",
publisher = "Wiley-Blackwell",
number = "6",

}

Niemann, S, Kanki, H, Fukui, Y, Takao, K, Fukaya, M, Hynynen, MN, Churchill, MJ, Shefner, JM, Bronson, RT, Brown, RH, Watanabe, M, Miyakawa, T, Itohara, S & Hayashi, Y 2007, 'Genetic ablation of NMDA receptor subunit NR3B in mouse reveals motoneuronal and nonmotoneuronal phenotypes', European Journal of Neuroscience, vol. 26, no. 6, pp. 1407-1420. https://doi.org/10.1111/j.1460-9568.2007.05774.x

Genetic ablation of NMDA receptor subunit NR3B in mouse reveals motoneuronal and nonmotoneuronal phenotypes. / Niemann, Stephan; Kanki, Hiroaki; Fukui, Yasuyuki; Takao, Keizo; Fukaya, Masahiro; Hynynen, Meri N.; Churchill, Michael J.; Shefner, Jeremy M.; Bronson, Roderick T.; Brown, Robert H.; Watanabe, Masahiko; Miyakawa, Tsuyoshi; Itohara, Shigeyoshi; Hayashi, Yasunori.

In: European Journal of Neuroscience, Vol. 26, No. 6, 01.09.2007, p. 1407-1420.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Genetic ablation of NMDA receptor subunit NR3B in mouse reveals motoneuronal and nonmotoneuronal phenotypes

AU - Niemann, Stephan

AU - Kanki, Hiroaki

AU - Fukui, Yasuyuki

AU - Takao, Keizo

AU - Fukaya, Masahiro

AU - Hynynen, Meri N.

AU - Churchill, Michael J.

AU - Shefner, Jeremy M.

AU - Bronson, Roderick T.

AU - Brown, Robert H.

AU - Watanabe, Masahiko

AU - Miyakawa, Tsuyoshi

AU - Itohara, Shigeyoshi

AU - Hayashi, Yasunori

PY - 2007/9/1

Y1 - 2007/9/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=34548666956&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34548666956&partnerID=8YFLogxK

U2 - 10.1111/j.1460-9568.2007.05774.x

DO - 10.1111/j.1460-9568.2007.05774.x

M3 - Article

C2 - 17880385

AN - SCOPUS:34548666956

VL - 26

SP - 1407

EP - 1420

JO - European Journal of Neuroscience

JF - European Journal of Neuroscience

SN - 0953-816X

IS - 6

ER -