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Investigation of the role of MHC class I molecule on the demyelination in a model of genetic demyelination

Research Project

Project/Area Number 09670806
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionOsaka University

Principal Investigator

TANIIKE Masako  Osaka University Medical School, Assistant Professor, 医学部, 助手 (30263289)

Co-Investigator(Kenkyū-buntansha) MATSUDA Yoshiko  Osaka University Hospital, Medical Staff, 医学部・附属病院, 医員
SHIMA Masaaki  Osaka University Medical School, Assistant Professor, 医学部, 助手 (10252660)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1998: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1997: ¥1,700,000 (Direct Cost: ¥1,700,000)
KeywordsGalactosylceramidase / Twitcher / MHC class I molecule / Apoptosis / lipocalin-type prostaglandin D synthase / MHC Class I分子 / リポカリン型プロスタグランディンD合成酵素 / twitcher
Research Abstract

The aim of this study was to investigate the role of upregulated MHC class I molecule in the demyelination of the twitcher, which is a murine model of genetic demyelinating disease, globoid cell leukodystrophy.The crossbreeding of beta2-microglobulin-knockout and twitcher mice makes us possible to start this project.The genotyping for both mutation has been established, however, there was a reproductive problem in F2 progeny.Thus, at present, we have not completed the observation.
We examined the pathomechanism possibly linked to the MHC-related cell recognition in the twitcher prototype and made several conclusions :
1) With progression of demyelination, mRNA for the genes encoding myelin basic protein, myelin-associated glycoprotein, proteolipid protein, and UDP-galactose : ceramide galactosyltransferase was downregulated in twitcher brains.
2) Morphological alterations of oligodendrocytes leading to their depletion were studied in the twitcher.Oligodendroglial cytoplasm as well as processes became shrunken with the progression of the disease and these were thought to be apoptotic by TUNEL labeling, DNA laddering and electron microscopical observation.
3) Expression of lipocalin-type prostaglandin D synthase (l-PGDS), an oligodendrocyte-associated protein, was examined in the twitcher brains.Unexpectedly, the enzyme is progressively upregulated during demyelination.Its distribution, which is inversely related to that of scavenger macrophages may suggest that l-PGDS may function to protect oligodendrocytes from degeneration.
Rodriguez et al.have been performed extensive studies about the pathological role of MHC class I on the demyelination using virus-induced demyelination and he suggested that the existence of this molecule is essential for the progression of demyelination and the occurrence of neurological deficits.Thus it is important to examine the forthcoming F2 and F3 progeny to see if his conclusion is also the case in this genetic demyelination.

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (6 results)

All Other

All Publications (6 results)

  • [Publications] M.Taniike et al.: "Suppressed UDP-galactose : ceramide galactosyltransferase and myelin protein mRNA in twitcher mouse brain" J Neurosci Res. 51. 536-540 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] M.Taniike et al.: "An apoptotic depletion of oligodendrocytes in the twitcher,a murine model of globoid cell leukodystrophy" J Neuropathol Exp Neurol. (in press). (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] M.Taniike et al.: "Suppressed UDP-galactose : ceramide galactosyltransferase and myelin protein mRNA in twitcher mouse brain." J Neurosci Res. 51. 536-540 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] M.Taniike et al.: "An apoptotic depletion of oligodendrocytes in the twitcher, a murine model of globoid cell leukodystrophy." J Neuropathol Exp Neurol. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] M.Taniike et al.: "Suppressed UDP-galactose:ceramide galactosyltransferase and myelin protein mKNA in twitcher mouse brain" J Neurosci Res. 51. 536-540 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] M.Taniike et al.: "An apoptotic depletion of oligodendrocytes in the twitcher,a murine model of globoid cell leukodystrophy" J Neuropathol Exp Neurol. in press. (1999)

    • Related Report
      1998 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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