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1994 Fiscal Year Final Research Report Summary

Preparation of mutant mice defective in the NMDA receptor channel

Research Project

Project/Area Number 05404085
Research Category

Grant-in-Aid for General Scientific Research (A)

Allocation TypeSingle-year Grants
Research Field Neurochemistry/Neuropharmacology
Research InstitutionUniversity of Tokyo (1994)
Niigata University (1993)

Principal Investigator

MISHINA Masayoshi  University of Tokyo, Faculty of Medicine, Professor, 医学部(医), 教授 (80144351)

Co-Investigator(Kenkyū-buntansha) SAKIMURA Kenji  Niigata University, Brain Research Institute, Associate Professor, 脳研究所, 助教授 (40162325)
Project Period (FY) 1993 – 1994
KeywordsNMDA receptor channel / epsilon1 subunit / Synaptic plasticity / Long-term potentiation / Spatial learning / Gene targeting / Hippocampus / Synaptic plasticity hypothesis of memory and learning
Research Abstract

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.

  • Research Products

    (52 results)

All Other

All Publications (52 results)

  • [Publications] Mori,H.: "Involvement of the carboxyl-terminal region in modulation by TPA of the NMDA receptor channel." NeuroReport. 4. 519-522 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yamakura,T.: "Different sensitivities of NMDA receptor channel subtypes to noncompetitive antagonists." NeuroReport. 4. 687-690 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Mishina,M.: "Molecular and functional diversity of the NMDA receptor channel." Ann.NY Acad.Sci.707. 136-152 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kawamoto,S.: "Expression of the α1 and α2 subunits of the AMPA-selective glutamate receptor channel in insect cells using a Baculovirus vector." Ann.NY Acad.Sci.707. 460-462 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Watanabe,M.: "Distinct spatio-temporal distributions of the NMDA receptor channel subunit mRNAs in the brain." Ann.NY Acad.Sci.707. 463-466 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Watanabe,M.: "Distinct distributions of five N-methyl-D-aspartate receptor channel subunit mRNAs in the forebrain." J.Comp.Neurol.338. 377-390 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yamakura,T.: "Phosphorylation of the carboxyl-terminal domain of the ζ1 subunit is not responsible for potentiation by TPA of the NMDA receptor channel." Biochem.Biophys.Res.Commun.196. 1537-1544 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takano,H.: "Chromosomal localization of the ε1,ε3 and ζ1 subunit genes of the human NMDA receptor channel." Biochem.Biophys.Res.Commun.197. 922-926 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Araki,K.: "Selective expression of the glutamate receptor channel δ2 subunit in cerebellar Purkinje cells." Biochem.Biophys.Res.Commun.197. 1267-1276 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Watanabe,M.: "Differential distributions of the NMDA receptor channel subunit mRNAs in the mouse retina." Brain Res.634. 328-332 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Watanabe,M.: "Distinct gene expression of the N-methyl-D-aspartate receptor channel subunit in peripheral neurons of the mouse sensory ganglia and adrenal gland." Neurosci.Lett.165. 183-186 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ishida,N.: "Circadian expression of NMDA receptor mRNAs,ε3 and ζ1,in the suprachiasmatic nucleus of rat brain." Neurosci.Lett.166. 211-215 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Watanabe,M.: "Distinct spatio-temporal expressions of five NMDA receptor channel subunit mRNAs in the cerebellum." J.Comp.Neurol.343. 513-519 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Watanabe,M.: "Distinct distributions of five NMDA receptor channel subunit mRNAs in the brainstem." J.Comp.Neurol.343. 520-531 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Watanabe,M.: "Distinct spatio-temporal distributions of the NMDA receptor channel subunit mRNAs in the mouse cervical cord." J.Comp.Neurol.345. 314-320 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nakano,R.: "A novel mutation in Cu/Zn superoxide dismutase gene in Japanese familial amyotrophic lateral sclerosis." Biochem.Biophys.Res.Commun.200. 695-703 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kaawmoto,S.: "Ligand binding properties and N-glycosylation of the α-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)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takahashi,H.: "Familial amyotrophic lateral sclerosis with a mutation in the Cu/Zn superoxide dismutase gene." Acta Neuropathol.88. 185-188 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tsuzuki,K.: "Ion permeation properties of the cloned mouse ε2/ζ1 NMDA receptor channel." Mol.Brain Res.26. 37-46 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hattori,S.: "Expression and characterization of the α2 subunit of the α-amino-3-hydroxy-5-methyl-4-isoxazole propionate(AMPA)-selective glutamate receptor channel in a Baculovirus system." Brain Res.666. 43-52 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Mori,H.: "Different spatio-temporal expressions of three otx homeoprotein transcripts during zebrafish embryogenesis." Mol.Brain Res.27. 221-231 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hirano,T.: "Involvement of the glutamate receptor δ2 subunit in the long-term depression of glutamate responsiveness in cultured Purkinje cells." Neurosci.Lett.182. 172-176 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sakimura,K.: "Reduced hippocampal LTP and spatial learning of mice lacking NMDA receptor ε1 subunit" Nature. 373. 151-155 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hirano,T.: "Suppression of LTD in cultured Purkinje cells deficient of glutamate receptor δ2 subunit" Neuro Report. (印刷中). (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kawamoto,S.: "N-linked glycosylation of the α-amino-3-hydroxy-5-methyl-4-isoxazole propいonate(AMPA)-selective glutamate receptor channel α2 subunit is essential fr the acquisition of ligand-binding activity." J.Neurochem.(印刷中). (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kawamoto,S.: "Expression and characterization of the zeta1 subunit of the N-methyl-D-aspartate(NMDA)receptor channel in a Baculovirus system." Mol.Brain Res.(印刷中). (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Mori, H.: "Involvement of the carboxyl-terminal region in modulation by TPA of the NMDA receptor channel." NeuroReport. 4. 519-522 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yamakura, T.: "Different sensitivities of NMDA receptor channel subtypes to noncompetitive antagonists." NeuroReport. 4. 687-690 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Mishina, M.: "Molecular and functional diversity of the NMDA receptor channel." Ann.NY Acad.Sci. 707. 136-152 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kawamoto, S.: "Expression of the alpha1 and alpha2 subunits of the AMPA-selective glutamate receptor channel in insect cells using a Baculovirus vector." Ann.NY Acad.Sci.707. 460-462 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Watanabe, M.: "Distinct spatio-temporal distributions of the NMDA receptor channel subunit mRNAs in the brain." Ann.NY Acad.Sci.707. 463-466 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Watanabe, M.: "Distinct distributions of five N-methyl-D-aspartate receptor channel subunit mRNAs in the forebrain." J.Comp.Neurol.338. 377-390 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yamakura, T.: "Phosphorylation of the carboxyl-terminal domain of the zeta1 subunit is not responsible for potentiation by TPA of the NMDA receptor channel." Biochem.Biophys.Res.Commun.196. 1537-1544 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] 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)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Araki, K.: "Selective expression of the glutamate receptor channel delta2 subunit in cerebellar Purkinje cells." Biochem.Biophys.Res.Commun.197. 1267-1276 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Watanabe, M.: "Differential distributions of the NMDA receptor channel subunit mRNAs in the mouse retina." Brain Res.634. 328-332 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Watanabe, M.: "Distinct gene expression of the N-methyl-D-aspartate receptor channel subunit in peripheral neurons of the mouse sensory ganglia and adrenal gland." Neurosci.Lett.165. 183-186 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ishida, N.: "Circadian expression of NMDA receptor mRNAs, epsilon3 and zeta1, in the suprachiasmatic nucleus of rat brain." Neurosci.Lett.166. 211-215 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Watanabe, M.: "Distinct spatio-temporal expressions of five NMDA receptor channel subunit mRNAs in the cerebellum." J.Comp.Neurol.343. 513-519 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Watanabe, M.: "Distinct distributions of five NMDA receptor channel subunit mRNAs in the brainstem." J.Comp.Neurol.343. 520-531 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Watanabe, M.: "Distinct spatio-temporal distributions of the NMDA receptor channel subunit mRNAs in the mouse cervical cord." J.Comp.Neurol.345. 314-320 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakano, R.: "A novel mutation in Cu/Zn superoxide dismutase gene in Japanese familial amyotrophic lateral sclerosis." Biochem.Biophys.Res.Commun.200. 695-703 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] 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)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takahasi, H.: "Familial amyotrophic lateral sclerosis with a mutation in the Cu/Zn superoxide dismutase gene." Acta Neuropathol.88. 185-188 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tsuzuki, K.: "Ion permeation properties of the cloned mouse epsilon2/zeta1 NMDA receptor channel." Mol.Brain Res.26. 37-46 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hattori, S.: "Expression and characterization of the alpha2 subunit of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) -selective glutamate receptor channel in a Baculovirus system." Brain Res.666. 43-52 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Mori, H.: "Different spatio-temporal expressions of three otx home oprotein transcripts during zebrafish embryogenesis." Mol.Brain Res.27. 221-231 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hirano, T.: "Involvement of the glutamate receptor delta2 subunit in the long-term depression of glutamate responsiveness in cultured Purkinje cells." Neurosci.Lett.182. 172-176 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sakimura, K.: "Reduced hippocampal LTP and spatial learning of mice lacking NMDA receptor epsilon1 subunit." Nature. 373. 151-155 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hirano, T.: "Suppression of LTD in cultured Purkinje cells deficient of glutamate receptor delta2 subunit." NeuroReport. (in press.).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kawamoto, S.: "N-linked glycosylation of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) -selective glutamate receptor channel alpha2 subunit is essential for the acquisition of ligand-binding activity." J.Neurochem.(in press.).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kawamoto, S.: "Expression and characterization of the zeta1 subunit of the N-methyl-D-aspartate (NMDA) receptor channel in a Baculovirus system." Mol.Brain Res.(in press.).

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1996-04-15  

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