Genetic ablation of NMDA receptor subunit NR3B in mouse reveals motoneuronal and nonmotoneuronal phenotypes.
Genetic ablation of NMDA receptor subunit NR3B in mouse reveals motoneuronal and nonmotoneuronal phenotypes.
复制标题
小鼠 NMDA 受体亚基 NR3B 的基因消融揭示了运动神经元和非运动神经元表型。
DOI：
10.1111/j.1460-9568.2007.05774.x
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Hayashi,Yas
中科院分区：
文献类型：
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作者：
Niemann,Stephan;Kanki,Hiroaki;Fukui,Yasuyuki;Takao,Keizo;Fukaya,Masahiro;Hynynen,MeriN;Churchill,MichaelJ;Shefner,JeremyM;Bronson,RoderickT;BrownJr,RobertH;Watanabe,Masahiko;Miyakawa,Tsuyoshi;Itohara,Shigeyoshi;Hayashi,Yas
NR3B是NMDA受体的一个调节亚单位，在头颅和脊髓的体细胞运动神经元中大量表达，在大脑的其他区域也有较低水平的表达。最近，我们发现人类NR3B基因(GRIN3B)具有高度的遗传异质性，在正常的欧美人群中，有10%的∼ 缺乏NR3B，这是由于该基因中存在纯合子的零等位基因。因此，了解NR3B基因缺失在人类和动物模型中的表型后果尤为重要。我们在这里提供了遗传缺失NR3B的小鼠的行为分析结果，由于遗传和环境背景的同质性，NR3B是一种理想的动物模型。NR3B-/-小鼠是活的和有生育能力的。与NR3B在躯体运动神经元中的表达一致，NR3B-/-小鼠在运动学习或协调方面表现出中度但严重的损害，并在其家庭笼子中活动减少。值得注意的是，NR3B-/-小鼠在家中与它们熟悉的笼友的社交互动高度增加，但在新环境中焦虑样行为适度增加，社交互动减少，这与NR3B对NMDA受体功能的抑制作用一致。这项工作是首次报道NR3Bin在活体中的功能意义，并可能深入了解NR3B的遗传变异在人类群体表型异质性中的贡献。
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 NR3Bin vivoand may give insight into the contribution of genetic variability of NR3B in the phenotypic heterogeneity among human population.