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2003 Fiscal Year Final Research Report Summary

Analysis of cerebellar function by using inducible mGluRl transgenic mice.

Research Project

Project/Area Number 14380368
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Neuroscience in general
Research InstitutionKobe University

Principal Investigator

AIBA Atsu  Kobe University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (20271116)

Co-Investigator(Kenkyū-buntansha) HARADA Takeshi  Kobe University, Graduate School of Medicine, Research Associate, 大学院・医学系研究科, 助手 (30362768)
MATSUDA Ikuo  Kobe University, Graduate School of Medicine, Research Associate, 大学院・医学系研究科, 助手 (50335452)
NODA Asao  Kobe University, Graduate School of Medicine, Research Associate, 大学院・医学系研究科, 講師 (40294227)
AIBA(FUSUSEN) Naomi (福泉 直美)  National Institute of Health and Nutrition, Senior Researcher, 主任研究員 (50199220)
Project Period (FY) 2002 – 2003
KeywordsmGluR1 / glutamate receptor / tetracycline / transgenic mice / L7 / Purkinje cell / cerebellum / hippocampus
Research Abstract

We planed to the role of mGluR1 in generation of neuronal network, synaptic, plasticity, and learning and memory by analysis of the mice, which conditionally express the mGluR1 in the specific brain region. In order to obtain these mice, we generated the mGluR1 transgenic mice in which expression of mGluR1 is regulated by tissue specific promoter and tetracycline or doxycylcine, using transcription factor tTA gene and tTA-responsible enhancer, TRE. We have obtained the following results.
1. Generation and analysis of NSE-tTA Tg/lacZ-TRE-mGluR1 Tg/mGluR1 (-/-) : This mice express the mGluR1 in cerebellar Purkinje cells but Tg expression did not rescue the motor discoordination observed in mGluR1 (-/-) mice.
2. Generation and analysis of CamKII-tTA Tg/lacZ-TRE-mGluR1a double Tg : These mice die at the ages of 3 to 4 weeks. They can survive and grow normally by application of paste food. The double Tg express mGluR1 mRNA in olfactory bulb, hippocampus CA1 area and striatum, suggesting the ectopic expression of mGluR1 in these regions is responsible for the lethality of the Tg mice.
3. Generation of the mice that express tTA in endogenous mGluR1 locus : Since ectopic expression of mGluR1 might lead mice to death, we introduced the tTA gene into mGluR1 locus by gene targeting. We have obtained mGluR1 (+/tTA) mice. Further, we generated 11 independent lines of TRE-mGluR1 Tg.
4. Generation of L7 (+/tTA) knock-in mice : We generated the mice that express tTA in cerebellar Purkinje cells. We also made DNA constructs for Tgs expressing TRE-PKCI or TRE-dominant negative MEK, which would inhibit PKC pathway or MAP kinase pathway, respectively.

  • Research Products

    (10 results)

All Other

All Publications (10 results)

  • [Publications] Kuwajima et al.: "Subcellular and subsynaptic localization of group I metabotropic glutamate receptors in the monkey subthalamic nucleus."J.Comp.Neurol.. 印刷中. (2004)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Chida et al.: "Disruption of protein kinase Cη results in impairment of wound healing and enhancement of tumor formation in mouse skin carcinogenesis."Cancer Res.. 第63巻・第10号. 2404-2408 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kishimoto et al.: "mGluR1 in cerebellar Purkinje cells is required for normal association of temporally contiguous stimuli in classical conditioning."Eur.j.Neurosci.. 第16巻・第12号. 2416-2424 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Muto et al.: "Pioglitazone treatment improved the cardiac and renal cystic phenotype of a targeted Pkd1 mutant."Hum.Mol.Genet.. 第11巻・第15号. 1731-1742 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tabata et al.: "Extracellular calcium controls the dynamic range of neuronal metabotropic glutamate receptor responses."Mol.Cell.Neurosci.. 第20巻・第1号. 56-68 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kuwajima, M., Hall, R.A., Aiba, A., Smith, Y.: "Subcellular and subsynaptic localization of group I metabotropic glutamate receptors in the monkey subthalamic nucleus."J.ComNeurol.. (in press). (2004)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Chida, K., Hara, T., Hirai, T., Konishi, C., Nakamura, K., Nakao, K., Aiba.A., Katsuki, M., Kuroki, T.: "Disruption of protein kinase Cη results in impairment of wound healing and enhancement of tumor formation in mouse skin carcinogenesis."Cancer Res.. 63-10. 2404-2408 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kishimoto, Y., Fujimichi, R., Araishi, K., Kawahara, S., Kano, M., Aiba, A., Kirino, Y.: "mGluR1 in cerebellar Purkinje cells is required for normal association of temporally contiguous stimuli in classical conditoning."Eur.J.Neunosci.. 16-12. 2416-2424 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Muto, S., Aiba, A., Saito, Y., Nakao, K., Nakamura, K., Tomita, K., Kitamura, T., Kurabayashi, M., Nagai, R., Higashihara, E., Harris, C., Katsuki, M., Horie, S.: "Pioglitazone treatment improved the cardiac and renal cystic phenotype of a targeted Pkd1 mutant."Hum.Mol.Genet.. 11-15. 1731-1742 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tabata, T., Aiba, A.Kano, M.: "Extracellular calcium controls the dynamic range of neuronal metabotropic glutamate receptor responses."Mol.Cell.Neunosci.. 20-1. 56-68 (2002)

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

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Published: 2005-04-19  

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