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Analysis of the pathogenesis of the hereditary non syndromic deafness caused by mutations in connection genes

Research Project

Project/Area Number 12470358
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Otorhinolaryngology
Research InstitutionNagasaki University

Principal Investigator

KIKUCHI Toshihiko  Nagasaki University School of Medicine, Depart,ment of Otolaryngology, Assistant Professor, 医学部・附属病院, 講師 (70177799)

Co-Investigator(Kenkyū-buntansha) TSUKASAKI Naoki  Nagasaki University School of Medicine, Depart,ment of Otolaryngology, Instructor, 医学部・附属病院, 助手 (70274660)
KOBAYASHI Toshimitsu  Nagasaki University School of Medicine, Depart,ment of Otolaryngology, Professor, 医学部, 教授 (80133958)
田中 藤信  長崎大学, 医学部, 助手 (00284688)
高村 博光  長崎大学, 医学部, 助手 (50281209)
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥14,100,000 (Direct Cost: ¥14,100,000)
Fiscal Year 2001: ¥6,700,000 (Direct Cost: ¥6,700,000)
Fiscal Year 2000: ¥7,400,000 (Direct Cost: ¥7,400,000)
Keywordsnonsyndromic deafness / inner ear / gap junction / connexin / voltage-gated potassium channel / Kv3.1b / Kv3.4 / aquaporin / non-syndromic deafness / gas junction / voltage-gated potassium channel / Kv3.4 / 遺伝性難聴 / 内リンパ電位 / 免疫組織化学
Research Abstract

1) Connexin 26 and connection 30 were expressed in both epithelial cell and connective tissue cell gap junction systems in the mammalian cochlea. In contrast, connection 31 was localized to the connective tissue cell gap junction system.
2) Voltage-gated potassium channel Kv3. 1 b-like immunoreactivity was present in the fibrocytes of the cochlear lateral wall. Immunostaining was also found in the interdental cells and the fibrocytes of the spiral limbus and in the supralimbal dark cells. Kv3.4-like immunoreactivity was present in the fibrocytes of the spiral ligament and the basal cells of the stria vascularis. In the organ of Corti, Kv3.4- like immunoreactivity was found in the hair cells and the neighboring supporting cells. The root cells and interdental cells were positively immunostained.
3) In the mammalian cochlea, aquaporin-1 and aquaporin-4 were found in some populations of the connective tissue cells and epithelial cells respectively.
4) The perilymphatlc per fusion with the long chain alcohol caused the depression of the endocochlear potential (FP). These findings suggested the functional significance of the gap junctional communication in the ion transporting mechanism in the mammalian cochlea.
5) In the mutant mouse lacking Brain-4, Na,K-ATPase-like immunoreactivity in the type II fibrocytes of the spiral ligament and the fibrocytes in the suprastrial zone was remarkably decreased. Connexin 26 was sparsely distributed among these fibrocytes in the cochlear lateral wall of this mutant mouse. These findings suggest that a dysfunction of fibrocytes and an interruption of the transcellular route via gap junctions can cause a depression of EP in the cochlea of this mutant mouse, and also suggest that the transcellular pathway via gap junctions plays a very important role in the transport of K+ ions in the cochlea.
6) Detailed physiological examinations were carried out in the cases of hereditary nonsyndromic deafness.

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • Research Products

    (21 results)

All Other

All Publications (21 results)

  • [Publications] T.Kikuchi, J.C.Adams, Y.Miyabe, B.So, T.Kobayashi: "Potassium ion recycling pathway via gap junction systems in the mammalian cochlea and its interruption in hereditary nonsyndromic deafness"Medical Electron Microscopy. 33. 51-56 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] A.-P.Xia, K.Ikeda, Y.Katori, T.Oshima, K.Kikuchi, T.Takasaka: "Expression of connexin 31 in the developing mouse cochlea"Neuroreport. 11. 2449-2453 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] S.A.Alam, K.Ikeda, T.Oshima, M.Suzuki, T.Kawase, T.Kikuchi, T.Takasaka: "Cisplatin-induced apoptotic cell death in Mongolian gerbil cochlea"Hearing Research. 141. 28-38 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 菊地俊彦: "遺伝子性難聴の内耳機構-カリウムイオン輸送機構の障害を中心に-"JOHNS. 17. 22-24 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] A.-P.Xia, Y.Katori, T.Oshima, K.Watanabe, T.Kikuchi, K.Ikeda: "Expression of connexin 30 in the developing mouse cochlea"Brain Research. 898. 27-29 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] E.So, T.Kikuchi, K.Ishimaru, Y.Miyabe, T.Kobayashi: "Immunolocalization of voltage-gated potassium channel Kv3.1b subunit in the cochlea"NeuroReport. 12. 2761-2765 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] A.-P.Xia, T.Kikuchi, O.Minowa, Y.Katori, T.Oshima, T.Noda, K.Ikeda: "Late-onset hearing loss in a mouse model of DFN3 nonsyndromic deafness : Morphologic and immunohistochemical analyses"Hearing Research. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] T. Kikuchi, J.C. Adams, Y. Miyabe, E. So, T. Kobayashi: "Potassium ion recycling pathway via gap junction systems in the mammalian cochlea and its interruption in hereditary non syndromic deafness"Medical Electron Microscopy. 33. 51-56 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] A.-P. Xia, K. Ikeda, Y. Katori, T. Oshima, T. Kikuchi, T. Takasaka: "Expression of connection 31 in the developing mouse cochlea"Neuro Report. 11. 2449-2453 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] S.A. Alam, K. Ikeda, T. Oshima, M. Suzuki, T. Kawase, T. Kikuchi, T. Takasaka: "Cisplatin-induced apoptotic cell death in mongolian gerbil cochlea"Hearing Research. 141. 28-38 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] T. Kikuchi: "Hereditary deafness caused by the interruption of the potassium ion recycling mechanism in the cochlea"JOHNS. 17. 22-24 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] A.-P. Xia, Y. Katori, T. Oshima, K. Watanabe, T. Kikuchi, K. Ikeda: "Expression of connection 30 in the developing mouse cochlea"Brain Research. 8i98. 364-367 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] E. So, T. Kikuchi*, K. Ishimaru, Y. Miyabe, T. Kobayashi: "Immunolocalization of voltage-gated potassium channel Kv3.1b subunit in the cochlea"Neuro Report. 12. 2761-2765 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] A.-P. Xia, T. Kikuchi, O. Minowa, Y. Katori, T. Oshima, T. Noda, K. Ikeda: "Late-onset hearing loss in a mouse model of DFN3 non syndromic deafness : Morphologic and analyses"Hearing Research. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] A.-p.Xia, Y.Katori, T.Oshima, K.Watanabe, T.Kikuchi, K.Ikeda: "Expression of connexin 30 in the developing mouse cochlea"Brain Research. 898. 27-29 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] E.So, T.Kikuchi, K.Ishimaru, Y.Miyabe, T.Kobayashi: "Immunolocalization of voltage-gated potassium channel Kv3.1b subunit in the cochlea"NeuroReport. 12. 2761-2765 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] A, -p.Xia, T.Kikuchi, O.Minowa, Y.katori, T.Oshima, T.Noda, K.Ikeda: "Late-onset hearing loss in a mouse model of DFN3 nonsyndromic deafness : Morphologic and immunohistochemical analyses"Hearing Research. (in press).

    • Related Report
      2001 Annual Research Report
  • [Publications] Xia A-P,Ikeda K,Katori Y,Oshima T,Kikuchi T,Takasaka T: "Expression of connexin 31 in the developing mouse cochlea"Neuroreport. 11. 2449-2453 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kikuchi T,Adams JC,Miyabe Y,So E,Kobayashi T: "Potassium ion recycling pathway via gap junction systems in the mammalian cochlea and its interruption in hereditary nonsyndromic deafness"Medical Electron Microscopy. 33. 51-56 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 菊地俊彦: "遺伝性難聴の内耳機構-カリウムイオン輸送機構の障害を中心に-"JOHNS. 17. 22-24 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Xia A-P,Katori Y,Oshima T,Watanabe K,Kikuchi T,Ikeda K: "Expression of connexin 30 in the developing mouse cochlea"Brain Research. (in press).

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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