Preparation of mutant mice defective in the NMDA receptor channel

NMDA受体通道缺陷突变小鼠的制备

• 批准号: 05404085
• 负责人: MISHINA Masayoshi
• 金额: $ 14.34万
• 依托单位: University of Tokyo (1994)Niigata University (1993)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (A)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-05404085/
• 关键词: NMDA receptor channel; epsilon1 subunit; Synaptic plasticity; Long-term potentiation; Spatial learning; Gene targeting; Hippocampus; Synaptic plasticity hypothesis of memory and learning; 記憶; 学習; シナプス形成; 遺伝子ノックアウト; ES細胞

The N-methyl-D-aspartate (NMDA) receptor channel plays a key role in synaptic plasticity, which is thought to underlie learning, memory and development. The NMDA receptor channel is formed by at least two members of the glutamate receptor (GluR) channel subunit families, that is, the GluRepsilon and GluRzeta subunit families. The four epsilon subunits are distinct in distribution, properties and regulation. Based on the Mg^<2+> sensitivity and expression patterns, we have proposed that the epsilon1 and epsilon2 subunits play a role in synaptic plasticity. Here we show that targeted disruption of the mouse epsilon1 subunit gene resulted in significant reduction of the NMDA receptor channel current and long-term potentiation (LTP) at the hippocampal CA1 synapses. The mutant mice also showed moderate deficiency in spatial learning. These results support the notion that the NMDA receptor channel-dependent synaptic plasticity is the cellular basis of certain forms of learning.

N-甲基-D-天冬氨酸（NMDA）受体通道在突触可塑性中起关键作用，这被认为是学习，记忆和发展的基础。 NMDA受体通道至少由谷氨酸受体（Glur）通道亚基家族的至少两个成员形成，即Glurepsilon和Glurzeta亚基家族。四个Epsilon亚基在分布，性质和调节方面是不同的。基于Mg^<2+>敏感性和表达模式，我们提出Epsilon1和Epsilon2亚基在突触可塑性中起作用。在这里，我们表明，靶向破坏小鼠Epsilon1亚基基因导致海马CA1突触上NMDA受体通道电流和长期增强（LTP）的显着降低。突变小鼠在空间学习方面还表现出适度的缺乏。这些结果支持以下观点：NMDA受体通道依赖性突触可塑性是某些形式学习形式的细胞基础。

项目成果

Kawamoto, S.: "Ligand binding properties and N-glycosylation of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) -selective glutamate receptor channel expressed in a Baculovirus system." Eur.J.Biochem.223. 665-673 (1994)

Kawamoto, S.：“杆状病毒系统中表达的 α-氨基-3-羟基-5-甲基-4-异恶唑丙酸酯 (AMPA) 选择性谷氨酸受体通道的配体结合特性和 N-糖基化。”

Watanabe, M.: "Distinct spatio-temporal distributions of the NMDA receptor channel subunit mRNAs in the brain." Ann.NY Acad.Sci.707. 463-466 (1993)

Watanabe, M.：“大脑中 NMDA 受体通道亚基 mRNA 的独特时空分布。”

Ishida, N.: "Circadian expression of NMDA receptor mRNAs, epsilon3 and zeta1, in the suprachiasmatic nucleus of rat brain." Neurosci.Lett.166. 211-215 (1994)

Ishida, N.：“大鼠大脑视交叉上核中 NMDA 受体 mRNA、epsilon3 和 zeta1 的昼夜节律表达。”

Nakano,R.et al.: "A novel mutation in Cu/Zn superoxide dismutase gene in Japanese familial amyotrophic lateral sclerosis" Biochem.Biophys.Res.Commun.(in press). (1994)

Nakano,R.等人：“日本家族性肌萎缩侧索硬化症中铜/锌超氧化物歧化酶基因的新突变”Biochem.Biophys.Res.Commun.（正在印刷中）。

Takano, H.: "Chromosomal localization of the epsilon1, epsilon3 and zeta1 subunit genes of the human NMDA receptor channel." Biochem.Biophys.Res.Commun.197. 922-926 (1993)

Takano, H.：“人类 NMDA 受体通道的 epsilon1、epsilon3 和 zeta1 亚基基因的染色体定位。”