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Study of G-protein-coupled potassium channel using a transgenic approach

Research Project

Project/Area Number 08680855
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurochemistry/Neuropharmacology
Research InstitutionTokyo Institute of Psychiatry

Principal Investigator

NUKADA Toshihide  Tokyo Institute of Psychiatry, Department of Neurochemistry, Head of Department, 神経化学研究部門, 副参事研究員 (80189349)

Project Period (FY) 1996 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1997: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1996: ¥1,400,000 (Direct Cost: ¥1,400,000)
KeywordsPotassium channel / G-protein / sulfonylures receptor / K_<ATP> / Transgenic mouse / Ted expression system / ムスカリン性K^+チャンネル / 内向き整流性K^+チャンネル / BIRチャンネル / GIRK1チャンネル / テトラサイクリン反応性発現
Research Abstract

To understand the physiological roles of G-protein-coupled potassium channels in brain, transgenic mice expressing K_<ATP> (Kir 6.2) and sulfonylurea receptor (SUR1) were generated. Kir 6.2 or SUR1 cDNA was inserted downstream of the tetracycline-regulated promoter region as the transgene vector, and the expression unit was excised from the resulting plasmid. These expression units were microinjected into fertilized eggs of BDF1 mice by the standard procedures. Transgenic mice were selected from possible founders by polymerase chain reaction and Southern blot analysis, ans were backcrossed to BDF1 mice. Two transgenic lines were established. To regulate the expression of Kir 6.2 and SUR1 by tetracycline, two transgenic lines overexlpressing O binding transactivator (tTA) were also established. Litter sizes and postneonatal development were indistinguishable from nontransgenic litter-mate controls in Kir 6.2-transgenic lines. However, both two SUR1-transgenic lines showed growth retardation and subsequent neonatal death, which were severer in homozygous mutant mice than in heterozygous mice. Thus, it was suggested that the transgenic phenotype was due to transgenic expression of SUR1, and not due to an insertional effect. In order to reveal the primary cause of death, we are now investigating the mutant mice in both pathological and biochemical aspects, in particular, focusing on the plasma levels of insulin and glucose.

Report

(3 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • Research Products

    (29 results)

All Other

All Publications (29 results)

  • [Publications] Nakamura, K.et al.: "Importance of N-terminal regions of G protein a subunits for the activation of phospholipase C in Xenopus oocytes." J.Biochem.120. 996-1001 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Nishi, M.et al.: "Unrestrained nociceptive response and disregulation of hearing ability in mice lacking nociceptin/orphanin FQ receptor." EMBO J.16. 1858-1864 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Furukawa, T.et al.: "Voltage and pH dependent block of cloned N-type Ca^<2+> channels by amlodipine." Br.J.Pharmacol.121. 1136-1140 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Furukawa, T.et al.: "Differential interactions of the C-terminus and the cytoplasmic I-II loop of neuronal Ca^<2+> channels with G-protein α- and βy-subunits:I.Molecular determination." J.Biol.chem.273(in press). (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Furukawa, T.et al.: "Differential interactions of the C-terminus and the cytoplasmic I-II loop of neuronal Ca^<2+> channels with G-protein α- and βy-subunits: II.Evidence for direct binding." J.Biol.chem.273(in press). (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 額田 敏秀: "Gタンパク質による内向き整流K^+チャンネルの直接的な調節機構" 生化学. 68. 1554-1559 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 額田 敏秀: "G蛋白質によるN型Ca^<2+>チャンネル調節機構に対するNefiracetamの作用一分子生物学の立場から" 精神医学. 38. 1337-1341 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 今井 公文、額田 敏秀: "分裂病遺伝子" 精神科治療学. 12. 1386-1387 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 額田 敏秀: "Gタンパク質" 脳の科学. 20. 476-477 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Nakamura, K., Nukada, T., Imai, K.and Sugiyama, H.: "Importance of N-terminal regions of G protein alpha subunits for the activation of phospholipase C in Xenopus oocytes." J.Biochem. 120. 996-1001 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Nishi, M., Houtani, T., Noda, Y., Mamiya, T., Sato, K., Doi, T., Kuno, J., Takeshima, H., Nukada, T., Nabeshima, T., Yamashita, T., Noda, T.and Sugimoto, T.: "Unrestrained nociceptive response and disregulation of hearing ability in mice lacking nociceptin/orphanin FQ receptor." EMBO J.16. 1858-1864 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Fukukawa, T., Nukada, T., Suzuki, K., Fujita, Y., Mori, Y., Nishimura, M.and Yamanaka, M.: "Voltage and pH dependent block of cloned N-type Ca^<2+> channels by amlodipine." Br.J.Pharmacol. 121. 1136-1140 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Furukawa, T., Nukada, T., Mori, Y., Wakamori, M., Fujita, Y., Ishida, H., Fukuda, K., Kato, S., and Yoshii, M.: "Differential interactions of the C-terminus and the cytoplasmic I-II loop of neuronal Ca^<2+> channels with G-protein alpha- and GehComputer analysis of pbetagamma-subunits : I.Molecular determination." J.Biol.Chem.273, (in press). (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Furukawa, T., Miura, R., Mori, Y., Strobeck, M., Suzuki, K., Ogihara, Y., Asano, T., Morishita, R., Hashii, M., Higashida, H., Yoshii, M.and Nukada, T.: "Differential interactions of the C-terminus and teh cytoplasmic I-II loop of neuronal Ca^<2+> channels with G-protein alpha-protein and betagammaisubunits : II.Evidence for direct binding." J.Biol, chem. 273, (in press). (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Nukada, T.: "Modulation of inwardly rectifying K^+ channels by G-proteins." Seikagaku. 68. 1554-1559 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Nukada, T.: "Effects of Nefiracetam on the modulation of Ca^<2+> channels by G-proteins." Seishin-igaku. 38. 1337-1341 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Imai, K.and Nukada, T.: "Genetic background of schizophrenia" seishinka chiryogaku. 12. 1386-1387 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Nukada, T.: "G-protein" No no kagaku. 20. 476-477 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Houtani,T.et al.: "Structure and regional distribution of nociceptin/orphanin FQ precursor." Biochem.Biophys.Res.Commun.219. 714-719 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Nakamura,K.et al.: "Importance of N-terminal regions of G protein α subunits for the activation of phospholipase C in Xenopus oocytes." J.Biochem.120. 996-1001 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Nishi,M.et al.: "Unrestrained nociceptive response and disregulation of hearing ability in mice lacking nociceptin/orphanin FQ receptor." EMBO J.16. 1858-1864 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Furukawa,T.et al.: "Voltage and pH dependent block of cloned N-type Ca^<2+> channels by amlodipine." Br.J.Pharmacol.121. 1136-1140 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 額田敏秀: "Gタンパク質による内向き整流K^+チャンネルの直接的な調節機構" 生化学. 68. 1554-1559 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] 額田敏秀: "G蛋白質によるN型Ca^<2+>チャンネル調節機構に対するNefiracetamの作用-分子生物学の立場から" 精神医学. 38. 1337-1341 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Houtani T., Nishi M. et al.: "Structure and regional distribution of nociceptin / orphanin FQ precursor." Biochem. Biophys. Res. Commun.219. 714-719 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Nakamura K., Nukada T. et al.: "Importance of N-terminal regions of G protein α subunits for the activation of phospholipase C in Xenopus oocytes." J. Biochem.120. 996-1001 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Nishi M., Nukada T. et al.: "Unrestrained nociceptive response and disregulation of hearing ability in mice lacking nociceptin / orphanin FQ receptor." EMBO J.(in press.). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] 額田敏秀: "Gタンパク質による内向き整流K^+チャンネルの直接的な調節機構." 生化学. 68. 1554-1559 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 額田敏秀: "G蛋白質によるN型Ca^<2+>チャンネル調節機構に対するNefiracetamの作用-分子生物学の立場から" 精神医学. 38. 1337-1341 (1996)

    • Related Report
      1996 Annual Research Report

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

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