2001 Fiscal Year Annual Research Report

自己免疫疾患ランバート・イートン筋無力症モデル動物の開発と病因メカニズムの解析

Research Project

Project/Area Number	12557216
Research Institution	The University of Tokyo
Principal Investigator	桐野豊東京大学, 大学院・薬学系研究科, 教授 (10012668)
Co-Investigator(Kenkyū-buntansha)	松尾亮太東京大学, 大学院・薬学系研究科, 助手 (40334338) 渡邊恵東京大学, 大学院・薬学系研究科, 助手 (80302610) 川原茂敬東京大学, 大学院・薬学系研究科, 助教授 (10204752) 川上善之エーザイ(株), 筑波研究所, 主幹研究員佐藤一紀福岡女子大学, 人間環境部, 教授 (10326473)
Keywords	神経筋接合部 / 自己免疫疾患 / カルシウムチャネル / マウス
Research Abstract	1.P型Caチャネルの細胞外に露出していると思われる、α1AサブユニットのドメインIVのS5セグメントとS6の間の20アミノ酸相当するに相当するペプチドを抗原としてうさぎを免疫し、ポリクローナル抗体を得た。この抗血清はP型Caチャネルをstableに発現させたHEK293細胞のlysateに対するウェスタンブロットにおいて、P型Caチャネルを特異的に認識することを確認した。 2.P型Caチャネルを強制発現させたHEK293細胞にP型Caチャネル特異的なペプチド毒ω-agato xinIVAに蛍光ラベルしたプローブを作用させ、蛍光顕微鏡下での観察を試みた。しかしこれまでに有効な結果は得られていない。 3.マウス横隔膜神経筋接合部プレシナプスからのアセチルコリン放出の修飾機構を調べる一環として、ムスカリン受容体サブタイプ欠損マウスの微小終板電位(MEPP)を調べた。M1欠損マウスにおいて、MEPPの頻度の有意な低下が認められた。MEPPの振幅は同腹の野生型マウスと同じであった。この結果は、プレシナプスからのアセチルコリンの放出がM1サブタイプ受容体によって促進されることを示唆する。 4.マウス横隔膜神経筋接合部に対するアセチルコリンエステラーゼ阻害薬E2020の効果を電気生理学的に検討した。その結果、MEPPおよびEPPの振幅の増大が認められた。K^+チヤネル阻害薬である4-aminopyrdineと一緒に投与する事によりその効果は促進された。

Research Products
(19 results)

All Other

All Publications (19 results)

[Publications] Tadashi Nakaya: "Expression and Function of a Novel Gene in Odor-taste Associative Learning in the Terrestrial Slug"Genes Cells. 6. 43-56 (2001)
[Publications] Yasushi Kishimoto: "Long-trace Interval Eyeblink Conditioning Is Impaired in Mutant Mice Lacking NMDA Receptor Subunit ε1"Eur.J.Neurosci.. 13. 1221-1227 (2001)
[Publications] Yasushi Kishimoto: "Classical Eyeblink Comditioning in Glutamate Receptor Subunit δ2 Mutant Mice Is Impaired in Delay Paradigm But Not in Trace Paradigm"Eur.J.Neursci.. 13. 1249-1253 (2001)
[Publications] Satoshi Watanabe: "Modulation of Oscillatory Neural Activities by Cholinergic Activation of Interneurons in the Olfactory Center of a Terrestrial Slug"Brain Res.. 896. 30-35 (2001)
[Publications] Kazuyasu Shindo: "Solution Structure of Micelle-bound H5 Peptide (427-452) : A Primary Structure Corresponding to the Pore-Forming Region of the Voltage Dependent Potassium Channel"Biochim.Biophys.Acta. 1545. 153-159 (2001)
[Publications] Yasushi Satoh: "β-Amyloid peptides inhibit acetylcholine release from cholinergic presynaptic nerve endings isolated from an electric ray"Neurosci.Lett.. 302. 97-100 (2001)
[Publications] Tsuyoshi Inoue: "Serotonin and NO Complementarily Regulate Generation of Oscillatory Activity in the Olfactory CNS of a Terrestrial Mollusk"J.Neurophysiol.. 85. 2634-2638 (2001)
[Publications] Kanako Takatsuki: "Effects of the noncompetitive NMDA receptor antagonist MK-801 on classical eyeblink conditioning in mice"Neurophamacol. 41. 618-628 (2001)
[Publications] Kanae Ando: "Phosphorylation-dependent regulation of the interaction of amyloid precursor protein with Fe65 affects the production of β-amyloid"J.Biol.Chem.. 276. 40353-40361 (2001)
[Publications] Yasushi Kishimoto: "Impaired delay but normal trace eyeblink conditioning in PLCβ4 mutant mice"Neuroreport. 12. 2919-2922 (2001)
[Publications] Yasushi Kishimoto: "Age-dependent impairment of delay and trace eyeblink conditioning in mice"Neuroreport. 12. 3349-3352 (2001)
[Publications] Yasushi Kishimoto: "Impairment of eyeblink conditioning in GluRδ2 mutant mice depends on the temporal overlap between conditioned and unconditioned stimuli"Eur.J.Neurosci.. 14. 1515-1521 (2001)
[Publications] Moritoshi Hirono: "Phospholipase Cβ4 and Protein Kinase Cα and/or Protein Kinase CβI Are Involved in the Induction of Long-Term Depression in Cerebellar Purkinje Cells"J.Biol.Chem.. 276. 45236-45242 (2001)
[Publications] Satoshi Shimozono: "Identification and characterization of an output neuron from the oscillatory molluscan olfactory network"Brain Res.. 921. 98-105 (2001)
[Publications] Yoshinori Muto: "Blepharismin, produced by the protozoan, Blepharisma japonicum, form ion-permeable channels in planar lipid bilayer membranes"FEBS Lett. 508. 423-426 (2001)
[Publications] Kanako Takatsuki: "Scopolamine impairs eyeblink conditioning in the cerebellar LTD-deficient mice"NeuroReport. 13. 159-162 (2002)
[Publications] Kanako Takatsuki: "Hippocampal damage disrupts eyeblink conditioning in mice lacking glutamate receptor subunit δ2"J.Biol.Phys.. (in press). (2002)
[Publications] Yasuko Inokuma: "Two Types of Network Oscillations and Their Odor Responses in the Primary Olfactory Center of a Terrestrial Mollusk"J.Neurophysiol.. (in press). (2002)
[Publications] 桐野豊: ""働く脳と変化する脳"「新生物物理の最前線」生物物理学会編,講談社ブルーバックス,pp.197-237"講談社. 203 (2001)

2001 Fiscal Year Annual Research Report

自己免疫疾患ランバート・イートン筋無力症モデル動物の開発と病因メカニズムの解析

Principal Investigator

桐野 豊 東京大学, 大学院・薬学系研究科, 教授 (10012668)

Research Products

[Publications] Tadashi Nakaya: "Expression and Function of a Novel Gene in Odor-taste Associative Learning in the Terrestrial Slug"Genes Cells. 6. 43-56 (2001)

[Publications] Yasushi Kishimoto: "Long-trace Interval Eyeblink Conditioning Is Impaired in Mutant Mice Lacking NMDA Receptor Subunit ε1"Eur.J.Neurosci.. 13. 1221-1227 (2001)

[Publications] Yasushi Kishimoto: "Classical Eyeblink Comditioning in Glutamate Receptor Subunit δ2 Mutant Mice Is Impaired in Delay Paradigm But Not in Trace Paradigm"Eur.J.Neursci.. 13. 1249-1253 (2001)

[Publications] Satoshi Watanabe: "Modulation of Oscillatory Neural Activities by Cholinergic Activation of Interneurons in the Olfactory Center of a Terrestrial Slug"Brain Res.. 896. 30-35 (2001)

[Publications] Kazuyasu Shindo: "Solution Structure of Micelle-bound H5 Peptide (427-452) : A Primary Structure Corresponding to the Pore-Forming Region of the Voltage Dependent Potassium Channel"Biochim.Biophys.Acta. 1545. 153-159 (2001)

[Publications] Yasushi Satoh: "β-Amyloid peptides inhibit acetylcholine release from cholinergic presynaptic nerve endings isolated from an electric ray"Neurosci.Lett.. 302. 97-100 (2001)

[Publications] Tsuyoshi Inoue: "Serotonin and NO Complementarily Regulate Generation of Oscillatory Activity in the Olfactory CNS of a Terrestrial Mollusk"J.Neurophysiol.. 85. 2634-2638 (2001)

[Publications] Kanako Takatsuki: "Effects of the noncompetitive NMDA receptor antagonist MK-801 on classical eyeblink conditioning in mice"Neurophamacol. 41. 618-628 (2001)

[Publications] Kanae Ando: "Phosphorylation-dependent regulation of the interaction of amyloid precursor protein with Fe65 affects the production of β-amyloid"J.Biol.Chem.. 276. 40353-40361 (2001)

[Publications] Yasushi Kishimoto: "Impaired delay but normal trace eyeblink conditioning in PLCβ4 mutant mice"Neuroreport. 12. 2919-2922 (2001)

[Publications] Yasushi Kishimoto: "Age-dependent impairment of delay and trace eyeblink conditioning in mice"Neuroreport. 12. 3349-3352 (2001)

[Publications] Yasushi Kishimoto: "Impairment of eyeblink conditioning in GluRδ2 mutant mice depends on the temporal overlap between conditioned and unconditioned stimuli"Eur.J.Neurosci.. 14. 1515-1521 (2001)

[Publications] Moritoshi Hirono: "Phospholipase Cβ4 and Protein Kinase Cα and/or Protein Kinase CβI Are Involved in the Induction of Long-Term Depression in Cerebellar Purkinje Cells"J.Biol.Chem.. 276. 45236-45242 (2001)

[Publications] Satoshi Shimozono: "Identification and characterization of an output neuron from the oscillatory molluscan olfactory network"Brain Res.. 921. 98-105 (2001)

[Publications] Yoshinori Muto: "Blepharismin, produced by the protozoan, Blepharisma japonicum, form ion-permeable channels in planar lipid bilayer membranes"FEBS Lett. 508. 423-426 (2001)

[Publications] Kanako Takatsuki: "Scopolamine impairs eyeblink conditioning in the cerebellar LTD-deficient mice"NeuroReport. 13. 159-162 (2002)

[Publications] Kanako Takatsuki: "Hippocampal damage disrupts eyeblink conditioning in mice lacking glutamate receptor subunit δ2"J.Biol.Phys.. (in press). (2002)

[Publications] Yasuko Inokuma: "Two Types of Network Oscillations and Their Odor Responses in the Primary Olfactory Center of a Terrestrial Mollusk"J.Neurophysiol.. (in press). (2002)

[Publications] 桐野 豊: ""働く脳と変化する脳"「新生物物理の最前線」生物物理学会編,講談社ブルーバックス,pp.197-237"講談社. 203 (2001)

桐野豊東京大学, 大学院・薬学系研究科, 教授 (10012668)

[Publications] 桐野豊: ""働く脳と変化する脳"「新生物物理の最前線」生物物理学会編,講談社ブルーバックス,pp.197-237"講談社. 203 (2001)