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Alternated splicing of tau in development and neurodegenerating disorders with dementia.

Research Project

Project/Area Number 16590841
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurology
Research InstitutionOsaka City University

Principal Investigator

TAKUMA Hiroshi  Osaka City University, Graduate School of Medicine, research associate, 大学院・医学研究科, 助手 (00326258)

Co-Investigator(Kenkyū-buntansha) MORI Hiroshi  Osaka City University, Graduate School of Medicine, professor, 大学院・医学研究科, 教授 (10159189)
TOMIYAMA Takami  Osaka City University, Graduate School of Medicine, lecturer, 大学院・医学研究科, 講師 (10305633)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2005: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000)
Keywordstau / FTDP-17 / exon 17 / splicing / dementia / アミロイド蛋白 / 細胞死 / アポトーシス / カスパーゼ3 / TUNEL / 細胞毒性
Research Abstract

Tau is one of the microtubule-associated proteins (MAPs) that play a role in promoting the polymerization and stabilization of neuronal microtubules and is involved in both the maintenance of the neuronal cytoskeleton and axonal transport. Human tau is encoded by a single gene (TAU) on chromosome 17 from which six isoforms are produced in the adult brain by alternative splicing of exons 2, 3 and 10. Tau exon 10 (E10) encodes the second microtubule-binding domain, and alternative splicing of this exon results in isoforms with three (E10-) or four (E10+) microtubule-binding domains referred to as three-repeat tau (3R-tau) and four-repeat tau (4R-tau), respectively. 4R-tau binds microtubules more avidly than 3R-tau due to its additional microtubule-binding domain encoded with E10. In human brains, only 3R-tau is expressed in the fetal stage while both 3R-tau and 4R-tau are expressed in a ratio of approximately 1:1 in the adult stage. In contrast, rodent brains express only 3R-tau in fetal and neonatal stages and only 4R-tau in the adult stage. Some mutations of the TAU gene found in frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) have been shown to affect alternative splicing of E10 and to thereby increase or decrease the ratio of 3R-tau to 4R-tau. Thus, as splicing of mouse E10 is different from human E10, the comparison of two genomic sequences is expected to provide a useful information. Genomic fragments were isolated from mouse genome libraries and compared with human sequence. We identified a new element in mouse intron 10 (I10) to suppress E10 splicing, which was located just after the stem-loop region previously proposed in human sequence and found to potentially form another stem-loop. Human I10 with a mutation (+29G to A) causing a decreased E10 splicing was also predicted to form similar double stem-loop, suggesting that this element is universally involved in regulation of E10 splicing.

Report

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

    (6 results)

All 2005 2004

All Journal Article (6 results)

  • [Journal Article] Regulation of tau exon 10 splicing by a double stem-loop structure in mouse intron 10.2005

    • Author(s)
      Takenari Yamashita
    • Journal Title

      FEBS Lett. 579

      Pages: 241-244

    • 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] Regulation of tau exon 10 splicing by a double stem-loop structure in mouse intron 10.2005

    • Author(s)
      Takenari Yamashita
    • Journal Title

      FEBS Letters 579

      Pages: 241-244

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Amyloid beta peptide-induced cerebral neuronal loss is mediated by casuase-3 in vivo.2004

    • Author(s)
      Hiroshi Takuma
    • Journal Title

      Journal of Neuropathology and Experimental Neurology 63(3)

      Pages: 255-261

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] A novel presenilin-1 mutation (Leu85Pro) in early-onset AD with spastic paraparesis.2004

    • Author(s)
      Suzuka Ataka
    • Journal Title

      Archives of Neurology 61(11)

      Pages: 1773-1776

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Amyloid beta peptide-induced cerebral neuronal loss is mediated by caspase-3 in vivo.2004

    • Author(s)
      Hiroshi Takuma
    • Journal Title

      Journal of Neuropathology and Experimental Neurology 63(3)

      Pages: 255-261

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Amyloid beta peptide-induced cerebral neuronal loss is mediated by caspase-3 in vivo2004

    • Author(s)
      Hiroshi Takuma, Takami Tomiyama, Keisuke Kuida, Hiroshi Mori
    • Journal Title

      Journal of Neuropathology and Experimental Neurology 63(3)

      Pages: 255-261

    • Related Report
      2004 Annual Research Report

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

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