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2003 Fiscal Year Final Research Report Summary

Analysis of the mechanism for neuronal degeneration and regeneration and responsible gene using the mutant mice disrupted of complex ganglioside

Research Project

Project/Area Number 14570118
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)

Co-Investigator(Kenkyū-buntansha) FURUKAWA Koichi  Nagoya University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (80211530)
HONDA Takashi  Fukushima Medical University, School of Medicine, Associate Professor, 医学部, 助教授 (20165608)
Project Period (FY) 2002 – 2003
Keywordsglycosyltransferase / acidic glycosphingolipids / ganglioside / knock out / degeneration of nervous system / sensory dysfunction / DNA microarray / GM2 / GD2 synthase gene
Research Abstract

We have cloned a number of glycosyltransferase cDNA, products of which are acidic glycosphingolipids (ganglioside), expressed mainly in the nerve system. We have also generated knock out (KO) mice to analyze the biological function of gangliosides. As a result, we found that complex gangliosides play an important role for survival and maintenance of the nervous system. In this study, we analyzed the genes, expression levels of which are different between the wild type and GM2/GD2 synthase gene KO mice using a comprehensive appriache DNA microarray.
We analyzed the chronological alteration of phenotypes in GM2/GD2 synthase gene KO mice and found the degeneration of nervous tissues in the dorsal horn of the spinal cord. Neurological examination revealed progressive sensory dysfunction with aging. We compared the mRNA expression in the spinal cord between the wild type and 20 weeks-old male KO mice by DNA microarray. mRNA expression levels of TGTP, IFI47,IFIT1,IRF7 and IRF1 were higher in KO mice than in the wild type mice. However, the difference in the expression levels was not significant. In the future, we will investigate the relation between these interferon-induced genes and the degeneration of the nervous system, and analyze the expression levels of these genes in older mice after onset of nervous system degeneration. Furthermore, we will prepare the RNA from degenerated sites in the spinal cord then analyze the gene expression profiles in the spinal cord of the wild type and KO mice.

  • Research Products

    (26 results)

All Other

All Publications (26 results)

  • [Publications] Kamimura, Y.: "Differential enhancing effects of α2,8-sialyltransferase on the cell proliferation and mobility"Int.J.Oncol.. (in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tsuchida, A.: "Synthesis of disialyl Lewis a structure in colon cancer cell lines by a sialyltransferase ST6GalNAc VI responsible for the synthesis of a-series gangliosides"J.Biol.Chem.. 278. 22787-22794 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Iwamura, K.: "The blood group P1 synthase gene is identical to the Gb3/CD77 synthase gene : A solution of the P1/P2/p puzzle."J.Biol.Chem.. 278. 44429-44438 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Furukawa, K.: "Isolation and functional analysis of the melanoma specific promoter region of human GD3 synthase gene."Biochim. Biophys. Acta.. 1627. 71-78 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Chen, H.H.: "Suppression of lung metastasis of mouse Lewis lung cancer P29 with transfection of the ganglioside GM2/GD2 synthase gene"Int.J.Cancer. 103. 169-176 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ma, Q., Kobayashi: "Morphological study of disordered myelination and the degeneration of nerve fibers in the spinal cord of mice lacking complex gangliosides"Arch. Histol. Cytol.. 66. 37-44 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Mitsuda, T.: "Over-expression of ganglioside GM1 results in the dispersion of platelet derived growth factor receptor from glycolipid-enriched microdomains and in the suppression of cell growth signals."J.Biol.Chem.. 277. 11239-11246 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Furukawa, K.: "Expression of the Gb3/CD77 synthase gene in megakaryoblastic leukemia cells : implication in the sensitivity to verotoxins."J.Biol.Chem.. 277. 11247-11254 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Inoue, M.: "Refractory skin injury in the complex knock-out mice expressing only GM3 ganglioside."J.Biol.Chem.. 277. 29881-29888 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Okada, M.: "b-senes ganglioside deficiency exhibits no definite change in the neurogenesis and the sensitivity to Fas-mediated apotosis, but impairs regeneration of the lesioned hypoglossal nerve."J.Biol.Chem.. 277. 1633-1636 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Bullens, R.W.M.: "Complex gangliosides at the neuromuscular junction are essential receptors for autoantibodies and botulinum neurotoxin but redundant for normal synaptic function."J.Neurosci. 22. 6876-6884 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nakamura, Y.: "Identification of a Drosophila gene encoding xylosylprotein B4-galactosyltransferase that is essential for the synthesis of glycosaminoglycan and for morphogenesis."J.Biol.Chem.. 277. 46280-46288 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 谷口 直之: "蛋白質・核酵・酵素 148"共立出版. 344 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kamimura, Y.: "Differential enhancing effects of α2,8-sialyltransferase on the cell proliferation and mobility."Int.J.Oncol.. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tsuchida, A.: "Synthesis of disialyl Lewis a structure in colon cancer cell lines by a sialyltransferase ST6Ga1NAc VI responsible for the synthesis of a-series gangliosides."J.Biol.Chem.. 278. 22787-22794 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Iwamura, K.: "The blood group P1 synthase gene is identical to the Gb3/CD77 synthase gene : A solution of the P1/P2/p puzzle."J.Biol.Chem.. 278. 44429-44438 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Furukawa, K.: "Isolation and functional analysis of the melanoma specific promoter region of human GD3 synthase gene."Biochim.Biophys.Acta.. 1627. 71-78 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Chen, H.H., Fukumoto, S.: "Suppression of lung metastasis of mouse Lewis lung cancer P29 with transfection of the ganglioside GM2/GD2 synthase gene."Int.J. Cancer. 103. 169-176 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ma, Q., Kobayashi: "Morphological study of disordered myelination and the degeneration of nerve fibers in the spinal cord of mice lacking complex gangliosides."Arch. Histol Cytol.. 66. 37-44 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Mitsuda, T.: "Over-expression of ganglioside GM1 results in the dispersion of platelet derived growth factor receptor from glycolipid-enriched microdomains and in the suppression of cell growth signals."J.Biol.Chem.. 277. 11239-11246 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Furukawa, K.: "Expression of the Gb3/CD77 synthase gene in megakaryoblastic leukemia cells : implication in the sensitivity to verotoxins."J.Biol.Chem.. 277. 11247-11254 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Inoue, M.: "Refractory skin injury in the complex knock-out mice expressing only GM3 ganglioside."J.Biol.Chem.. 277. 29881-29888 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Okada, M.: "b-series ganglioside deficiency exhibits no definite changes in the neurogenesis and the sensitivity to Fas-mediated apotosis, but impairs regeneration of the lesioned hypoglossal nerve."J.Biol.Chem.. 277. 1633-1636 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Bullens, R.W.M: "Complex gangliosides at the neuromuscular junction are essential receptors for autoantibodies and botulinum neurotoxin but redundant for normal synaptic function."J.Neurosci.. 22. 6876-6884 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakamura, Y.: "Identification of a Drosophila gene encoding xylosylprotein β4-galactosyltransferase that is essential for the synthesis of glycosaminoglycans and for morphogenesis."J.Biol.Chem.. 277. 46280-46288 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Taniguchi N.: "Protein・Nucleic acid・Enzyme 148"Kyouritsusyuppan. 344 (2003)

    • 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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