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Molecular genetic research on the peculiar form of Becker Muscular Dystrophy (BMD), where cardiac muscle is preferentially involved

Research Project

Project/Area Number 06670680
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Neurology
Research InstitutionNational Center of Neurology and Psychiatry

Principal Investigator

TAKEDA Shin-ichi  Dept.of Molecular Genetics, National Institute of Neuroscience, Section Chief, 神経研究所・遺伝子工学研究部, 室長 (90171644)

Co-Investigator(Kenkyū-buntansha) MIYAGOE Yuko  Dep.of Neuromuscular Research, National Institurte of Neuroscience, COE project-, 神経センター・神経研究所・疾病研究第一部, COE特別研究員
古賀 律子  国立精神, 神経センター・神経研究所・疾病研究第一部, センター研究員
Project Period (FY) 1994 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1995: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1994: ¥1,400,000 (Direct Cost: ¥1,400,000)
KeywordsMuscular dystrophy / DMD gene / Dystrophin / Cardiac involvement / transcriptional regulation / CArG box sequence / XLCM / 筋ジフトロフィー
Research Abstract

Cardiac muscle was preferentially involved in some patients of BMD,and we found the deletion of the DMD gene around intron 1 in these patients. We started further study based on the hypothesis that preferential cardiac involvement was due to aberrant transcriptional regulation of the DMD gene.
1) Incidence of the BMD families with cardiac involvement in Japan
We investigated the incidence of BMD families with cardiac involvement in Japan in collaboration with Department of Medicine in Shinsyu University. BMD patients with cardiac involvement who have the deletion between exon 45-48 of the DMD gene, showed typical skeletal muscle symptom for BMD.However the group of BMD patients with cardiac involvement, who revealed the deletion around the 5'-end of the DMD gene, often developed cardiac involvement without overt skeletal muscle symptom.
2) Analysis of the DMD gene of BMD family with cardiac involevement
We collected the BMD families, which show preferential cardiac involvement and the deletion around 5'-end of the gene. The molecular genetic study using DNA marker for intron 1 of the gene revealed that preferential cardiac involvement cannot be explained by the deletion of the particular part of the intron 1.
3) Transcriptional regulation of the DMD gene in cardiac muscle
We prepared the series of constructions which contain various lengths of the DMD gene promoter with CAT reporter gene. We transfected these constructs into the C2 cells or rat neonatal primary cardiac cells. The promoter construct, which has up to-102bp of the gene showed the highest activities in skeletal and cardiac cells. The fragment contained the CArG box sequence and the deletion or the mutation of the CArG box sequence leads the loss of activities in both cells.

Report

(3 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] Sekijima, Y. et al.: "A case of cytoplasmic myopathy with hypertrophic cardio・・・" Int Med. 34. 166-170 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yoshida, K. et al.: "A mutantion in the ceruloplasmin gene in associated with・・・" Nature Genet. 9. 267-272 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Takeda, S. et al.: "Myogenic regulatory factors can activate TATA-containing・・・" J. Biol. Chem.270. 15664-15670 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 武田伸一: "遺伝性筋疾患-病因遺伝子と病態との関連-" Brain and Nerve. 47. 735-748 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 武田伸一: "DMD遺伝子/ジストロフィンの異常と拡張型心筋症" 内科. 75. 441-446 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Nakamura A, Kojo T, Arahata K and Takeda S: "Reductions of serum IgG level and peripheral T cell counts are correlated with CTG repeat lengths in myotonic dystrophy patients" Neuromuscular Disorders. (in press). (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 武田伸一(分担執筆): "分子神経病学" 南光堂, in press (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 武田伸一(分担執筆): "臨床遺伝医学VI" 診断と治療社, 473 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Sekijima, Y. et al.: "A case of cytopassmic myopathy with hypertrophic…" Int Med. 34. 166-170 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Yoshida, K. et al.: "A mutant in the ceruloplasmin gene is associated with…" Nature Genet. 9. 267-272 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Takeda, S. et al.: "Myogenic regulatory factors can activate TATA-containing…" J. Biol. Chem.270. 15664-15670 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Nakamura, A. et al.: "Reducton of IgG and peripheral T cells…" Neuromuscular Disorders. (in press). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] 武田伸一: "遺伝性筋疾患-病因遺伝子と病態との関連-" Brain and Nerve. 47. 735-748 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 武田伸一: "DMD遺伝子/ジストロフィンの異常と拡張型心筋症" 内科. 75. 441-446 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 武田伸一(分担執筆): "分子神経病学" 南光堂(in press), (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] 武田伸一(分担執筆): "臨床遺伝医学VI" 診断と治療社, 473 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Sekijima,Y.et al.: "A case of cytoplasmic myopathy with hypertrophic ---" Jpn J Int Med. in press. (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Yoshida,K.et al.: "A mutant in the ceruloplasmin gene is associated with ---" Nature Genet. in press. (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Takeda,S.et al.: "Myogenic regulatory factors can activate TATA-containing promoter --" J.Biol.Chem.in press. (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] 宮越友子、他: "筋の発生・分化の分子機構" 小児科臨床. 47. 2439-2435 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 石井亜紀子,他: "デュシャンヌ型筋ジストロフィー/Duchenne muscular dystrophy" 実験医学. 12. 121-125 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 武田伸一: "DMD遺伝子/ジストロフィンの異常と拡張型心筋症" 内科. 75. 441-446 (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] 石井亜紀子(分担執筆): "クリニカル・ファーマシーのための内科学" 医薬ジャーナル社, 563 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 武田伸一(分担執筆): "臨床遺伝医学VI" 診断と治療社(印刷中), (1995)

    • Related Report
      1994 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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