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哺乳類の生得的行動を制御する遺伝要素の探索

Research Project

Project/Area Number 08878118
Research Category

Grant-in-Aid for Exploratory Research

Allocation TypeSingle-year Grants
Research Field Molecular biology
Research InstitutionOkazaki National Research Institutes

Principal Investigator

八木 健  岡崎国立共同研究機構, 生理学研究所, 助教授 (10241241)

Project Period (FY) 1996 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1998: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1997: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1996: ¥1,000,000 (Direct Cost: ¥1,000,000)
KeywordsFyw / CNR / カドヘリン / GABA / 行動 / 情動 / 学習 / シナプス / 脳の進化 / DBA / 2 / エタノール / Fyn / ジーンターゲティング / 生得的行動
Research Abstract

我々は哺乳類の生得的行動の分子メカニズムを解析する目的で、現在までに遺伝子欠損マウス作製により本能・情動行動の異常を示すFynに注目して解析してきた。本年度は更に1)情動行動異常を示すFyn欠損マウスの嗅球における電気生理学的異常の解析、2)マウス脳神経でFynと結合するレセプター分子の解析を行った。その結果、Fyn欠損マウスでは嗅球における電気生理学的長期増強がおこらず、またGABAA受容体のアンタゴニストに対する電気生理学的反応の減少が認められた。匂い刺激による哺乳行動の異常がFyn欠損マウスで認められることより、これらの電気生埋学的異常と行動異常との関わりが注目される。また、Fyn結合分子中での受容体型分子群の解析を行った結果、興味深いことに新たなカドヘリン型受容体(cadherin related neural receptor:CNR)がFynと結合していることが明らかとなった。このCNR分子はシナプスに局在しており、マウスで約20種類のファミリーであることが明らかとなった。Fynがシナプス機能を制御し情動・学習に関わることより、シナプスでFynと結合して存在する受容体分子の多様性がどの様にシナプス機能、神経回路形成、行動制御に関わるかについては興味深く、今後このCNRファミリーの生体内での分子機能に焦点を当て解析を行う予定である。

Report

(3 results)
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • 1996 Annual Research Report
  • Research Products

    (21 results)

All Other

All Publications (21 results)

  • [Publications] Takahashi,S.et al.: "Reduced hippocampal LTP in mice lacking a presynaptic protein:complexin II" Eur.J.Neurosci. (in press). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yanagawa,Y et al.: "Enrichment and efficient screening of ES cells containing a targeted mutation:the use of DT-A gene with the polyadenylation signal as a negative selection maker." Transgenic Research. (in press). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yagi,T: "Molecular mechanisms of Fyn-tyrosine kinase for regulating mammalian behaviors and an ethanol sensitivity" Biochemical Pharmacology. (in press). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Mori,H et al.: "Role of the carboxy-terminal region of the GluR2ε2 subunit in synaptic localization of the NMDA receptor channel" Neuron. 21. 571-580 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kohmura N et al.: "Diversity Revealed by a Novel Family of Cadherins Expressed in Neurons at Synaptic Complex" Neuron. 20. 1137-1151 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Taniguchi,M et al.: "Efficient production of Cre-mediated site-directed recombinants through the utilization of the puromycin resistance gene,pac:a transient gene-integration marker for ES cells." Nucleic Acids Res. 26. 679-680 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Taniguchi M.et al: "Efficient production of Cre-mediated site-directed recombinants throuth the utilization of the puromicin resistance gene,pac : a transient gene-integration marker for ES cells." Nucleic Acids Res. 26. 679-680 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kitazawa,H.et al: "Abnormal synaptic transmission in the olfactory bulb of Fyn-kinase deficient mice." J.Neurophysiol.79・1. 137-142 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Taniguchi,M.et al: "Disruption of semaphorin III/D gene causes severe abnormality in peripheral nerve projection." Neuron. 19. 519-530 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kai,N.et al: "Molecular cloning of Fyn-associated molecules in the mouce central nervous system." J.Neuroscience Res.48. 407-424 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Miyakawa,T.et al: "Fyn-kinase as a determinant of ethanol sencitvity : Relation to NMDA-receptor function." Sience. 278. 698-701 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 八木健: "脳の進化をもたらした遺伝子の探索-情動形成に関わる分子メカニズムによる研究-" 細胞工学. 16. 1140-1149 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Miyakawa,T.,Yagi,T.,Kagiyama,A.and Niki,H.: "Radial maze performance,open-field and elevated plus-maze behaviors in Fyn-kinase deficiedt mice ; Further evidence for increased fearfulness" Molecular Brain Research. 37. 145-150 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Miyakawa,T.,Yagi,T.,Tateishi,K.and Niki,H.: "Susceptibility to drug-induced seizures of Fyn tyrosine kinase-deficient mice" Neuroreport. 7. 2723-2726 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kutsuwada,T.,et al: "Impairment of suckling response,trigeminal neuronal pattern formation,and hippocampal LTD in NMDA receptor ε2 subunit mutant mice." Neuron. 16. 333-344 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Tezuka,T.,et al: "Physical and functional association of the cbl protooncogene product with an Src-family protein tyrosine kinase,p53/56lyn,in the B cell antigen receptor-mediated signaling." Journal of Experimental Medicine. 183. 675-680 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Yasunaga M.,et al: "Involvement of Fyn tyrosine kinase in progression of cytokinesis of B lymphocyte progenitor." Journal of Cell Biology. 132. 91-99 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Asada,H.,et al: "Mice lacking the 65 kDa isoform of glutamic acid decarboxylase (GAD65) maintain normal levels of GAD67 and GABA in their brains but are susceptible to seizures" Biochemical and Biophysical Research Communications. 229. 891-895 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kai,N.,et al: "Molecular cloning od Fyn-associated molecules in the mouse central nervous system" Journal of Neuroscience Research. in press (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] 三宝誠、谷口雅彦、八木健: "Cre-loxPを用いた新しい遺伝子変換マウス作製法" 組織培養. 22. 506-511 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 八木健等: "遺伝子導入動物の作製とその応用" 新生物化学実験のてびき. 4. 89-134 (1996)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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