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The mechanisms for the neuronal degeneration in the retina of the mutant mice lacking b-series acidic glycosphingolipids.

Research Project

Project/Area Number 16590243
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pathological medical chemistry
Research InstitutionNagoya University

Principal Investigator

FURUKAWA Keiko  Nagoya University, Graduate School of Medicine, Assistant Professor, 大学院・医学系研究科, 講師 (50260732)

Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2004: ¥2,200,000 (Direct Cost: ¥2,200,000)
Keywordsacidic glycosphingolipids / glycosyltransferase gene / glycosyltransferase gene defective mice / GD3 / retinal tissue / electroretinogram / 酸性スフィンゴ糖脂質 / 糖転換酵素遺伝子 / GD3合成酵素遺伝子欠損マウス / Laser Capture microdissection / 遺伝子発現
Research Abstract

We have performed molecular cloning of glycosyl transferase cDNA which are highly expressed in the nervous systems and are involved in the synthesis of acidic glycosphingolipids, gangliosides. In order to investigate the function of gangliosides, we have generated knock-out(KO) mice of various glycosyltransferase genes, and analyzed the abnormal phenotypes. Consequently, we have demonstrated that complex gangliosides were essential molecules in the maintenance of the nerve tissues.
In the present study, we generated GD3 synthase-KO mice and analyzed the role of b-series gangliosides in the retina tissues, since ganglioside GD3 is specifically expressed in murine retina suggesting into important roles.
The results were as follows,
1. Expression of b-series gangliosides in the murin retina.
In murine retina, GD3, GD1b and GT1b were highly expressed in the neurofibers, inner plexiform layer and inner nuclear layer.
2. Comparison of pathological findings in the retina between the wild type and GD3-KO mice.
After mating GD3-KO mice with C57BL/6 mice as a back cross manner, eye balles of the mice were fixed in formaldehyde, and stained with Hematoxylin-Eosin, then abnormalities in the retinal tissues were examined. In the GD3-KO mice, inner plexiform and inner nuclear layer were thinner than those in the wild type ; i.e. inner nuclear layer consisted of 4〜5 cells in the wild type, but just 3〜4 cells in the GD3-KO mice.
3. Examination of electroretinogram in GD3-KO mice.
Using the wild type and GD3-KO mice, electroretinogram was examined, resulting in no differences.
The GD3-KO mice lacking these b-series ganglioside showed no apparent abnormal morphology in these layer structures, but the thickness of the inner plexiform and inner nuclear layer became thin, suggesting that b-series gangliosides may be involved in the intact formation of the inner plexiform and inner nuclear layers.

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (25 results)

All 2005 2004

All Journal Article (24 results) Book (1 results)

  • [Journal Article] Ganglioside GD3 promotes cell growth and invasion through p130Cas and paxillin in malignant melanoma cells2005

    • Author(s)
      Hamamura, K.
    • Journal Title

      Proc. Natl. Acad. Sci. 102

      Pages: 11041-11046

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Mechanisms for the apoptosis of small cell lung cancer cells induced by anti-GD2 monoclonal antibodies : Roles of anoikis.2005

    • Author(s)
      Aixinjueluo, W.
    • Journal Title

      J. Biol. Chem. 280

      Pages: 29828-29836

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] GD3 synthase gene knockout mice exhibit thermal hyperalgesia and mechanical allodynia but decreased response to formalin-induced prolonged noxious stimulation.2005

    • Author(s)
      Handa, Y.
    • Journal Title

      Pain. 117

      Pages: 271-279

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Sensory nerve-dominant nerve degeneration and remodeling in the mutant mice lacking complex gangliosides.2005

    • Author(s)
      Sugiura, Y.
    • Journal Title

      Neuroscience 135

      Pages: 1167-1178

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Over-expression of GDla ganglioside sensitizes motor nerve terminals to anti-GDla antibody mediated injury in a model of acute motor axonal neuropathy.2005

    • Author(s)
      Goodfellow, J.
    • Journal Title

      J. Neurosci. 25

      Pages: 1620-1628

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Different response of the knockout mice lacking b-series gangliosides against botulinum and tetanus toxina.2005

    • Author(s)
      Kitamura, M.
    • Journal Title

      Biochim. Biophys. Acta. 1741

      Pages: 1-3

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Ganglioside GD3 promotes cell growth and invasion through p130Cas and paxillin in malignant melanoma cells.2005

    • Author(s)
      Hamamura, K.
    • Journal Title

      Proc.Natl.Acad.Sci.USA 102

      Pages: 11041-11046

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Mechanisms for the apoptosis of small cell lung cancer cells induced by anti-GD2 monoclonal antibodies : Roles of anoikis.2005

    • Author(s)
      Aixinjueluo, W.
    • Journal Title

      J.Biol.Chem. 280

      Pages: 29828-29836

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Over-expression of GD1a ganglioside sensitizes motor nerve terminals to anti-GD1a. antibody mediated injury in a model of acute motor axonal neuropathy.2005

    • Author(s)
      Goodfellow, J.
    • Journal Title

      J.Neurosci. 25

      Pages: 1620-1628

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Different response of the knockout mice lacking b-series gangliosides against botulinum and tetanus toxina.2005

    • Author(s)
      Kitamura, M.
    • Journal Title

      Biochim.Biophys.Acta. 1741

      Pages: 1-3

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Ganglioside GD3 promotes cell growth and invasion through p130Cas and paxillin in malignant melanoma cells.2005

    • Author(s)
      Hamamura, K.
    • Journal Title

      Proc.Natl.Acad.Sci. 102

      Pages: 11041-11046

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Over-expression of GD1a ganglioside sensitizes motor nerve terminals to anti-GD1a antibody mediated injury in a model of acute motor axonal neuropathy.2005

    • Author(s)
      Goodfellow, J.
    • Journal Title

      J.Neurosci. 25

      Pages: 1620-1628

    • Related Report
      2005 Annual Research Report
  • [Journal Article] GM1 expression in H-ras-transformed NIH3T3 results in the suppression of cell proliferation inducing the partial transfer of activated H-ras from non-ract to raft faction.2005

    • Author(s)
      Hamamura, K. et al.
    • Journal Title

      Int.J.Oncol. 26

      Pages: 897-904

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Over-expression of GD1a ganglioside sensitizes motor nerve terminals to anti-GD1a antibody mediated injuly in a model of acute motor axonal neuropathy.2005

    • Author(s)
      Goodfellow, John. et al.
    • Journal Title

      J.Neurosci 25

      Pages: 1620-1628

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Differential enhancing effects of α2,8-sialyltransferase on the cell proliferation and mobility.2005

    • Author(s)
      Kamimura Y. et al.
    • Journal Title

      Int.J.Oncol 26

      Pages: 337-344

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Overexpressed GM1 suppresses nerve growth factor(NGF) signals by modulating the intracellular localization of NGF receptors and membrane fluidity in PC12 cells.2004

    • Author(s)
      Nishio, M.
    • Journal Title

      J. Biol. Chem 279

      Pages: 33368-33378

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Innate murine B cells produce anti-disialosyl antibodies reactive with Campylobacter jejuni LPS and gangliosides that are polyreactive and encoded by a restricted set of unmutated V genes.2004

    • Author(s)
      Boffey, J.
    • Journal Title

      J. Neuroimmunol 152

      Pages: 98-111

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Glycosphingolipids in engineered mice : insights into function.2004

    • Author(s)
      Furukawa, K.
    • Journal Title

      Semin. Cell Dev. Biol 15

      Pages: 389-96

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Overexpressed GM1 suppresses nerve growth factor(NGF) signals by modulating the intracellular localization of NGF receptors and membrane fluidity in PC12 cells.2004

    • Author(s)
      Nishio, M.
    • Journal Title

      J.Biol.Chem. 279

      Pages: 33368-33378

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Innate murine B cells produce anti-disialosyl antibodies reactive with Campylobacter jejuni LPS and gangliosides that are polyreactive and encoded by a restricted set of unmutated V genes.2004

    • Author(s)
      Boffey, J.
    • Journal Title

      J.Neuroimmunol. 152

      Pages: 98-111

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Glycosphingolipids in engineered mice : insights into function.2004

    • Author(s)
      Furukawa, K.
    • Journal Title

      Semin.Cell Dev.Biol. 15

      Pages: 389-396

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Innate murine B cells produce anti-disialosyl antibodies reactive with Campylobacter jejuni LPS and gangliosides that are polyreactive and ancoded by a restricted set of unmutated V genes.2004

    • Author(s)
      Boffey, J. et al.
    • Journal Title

      J.Neuroimmunol. 152

      Pages: 98-111

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Glycosphingolipids in engineered mice : insights into function.2004

    • Author(s)
      Furukawa, Koichi. et al.
    • Journal Title

      Semin.Cell Dev.Biol. 15

      Pages: 389-396

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Over-expressed GM1 suppresses NGF signals by modulating the intra-cellular localization of NGF receptors and membrance fluidity in PC122004

    • Author(s)
      Nishio, Masashi. et al.
    • Journal Title

      J.Biol.Chem. 279

      Pages: 33368-333378

    • Related Report
      2004 Annual Research Report
  • [Book] 糖鎖遺伝子研究 1.14 糖脂質糖鎖の合成に関与する転移酵素遺伝子、未来を拓く糖鎖科学2005

    • Author(s)
      古川鋼一
    • Publisher
      金芳堂
    • Related Report
      2005 Annual Research Report

URL: 

Published: 2004-04-01   Modified: 2016-04-21  

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