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1994 Fiscal Year Final Research Report Summary

Studiy of effectiveness of gene therapy in lysosomnal storage disease

Research Project

Project/Area Number 05454289
Research Category

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

Allocation TypeSingle-year Grants
Research Field Pediatrics
Research InstitutionOsaka University

Principal Investigator

OKADA Shintaro  Osaka University, Dept.Pediatr., Prof., 医学部, 教授 (30028609)

Co-Investigator(Kenkyū-buntansha) FUKUSHIMA Hisao  Osaka University, Dept.Pediatr., Assist.Prof., 医学部, 助手 (70199214)
INUI Koji  Osaka University, Dept.Pediatr., Associate Prof., 医学部, 講師 (90175208)
Project Period (FY) 1993 – 1994
KeywordsKrabbe disease / twitcher mouse / mutation analysis / gene therapy / galactosylceramidase
Research Abstract

Krabbe disease (globoid cell leukodystrophy) is an autosomal recessive neurodegenerative disorder that affects both the central and the peripheral nervous system due to the enzymatic defect of galactocerebrosidase. Recently, we have succeeded in cloning the cDNA.In this study molecular defects in Krabbe disease were investigated in twelve patients (seven Japanese and five non-Japanese patients) using cultured skin fibroblasts. We found six types of point mutations and 3 types of deletions. The low enzymatic activity of the cDNAs with the three mutations, nonsense mutation at codon 369 in a non Japanese typical infantile patient, two misssense mutation (Pro at codon 302 to Ala, Val at codon 550 to Gly) in a japanese late infantile patient and non-Japanese patient, were confirmed in expression studies. The P302A mutation was heterozygous and the V550G was homozygous in genomic analysis. A twelve base deletion with 3 base insertion was found in three infantile Japanese patients and not found in 30 controls. The mutation was homozygous in two patients and heterozygous in a patient, resulting in the 36% allele frequency in Japanese patients. In this study we for the first time clarified the molecular defects in krabbe disease.

  • Research Products

    (10 results)

All Other

All Publications (10 results)

  • [Publications] Sakai,N.et al.: "Krablee diseae:isolation and characterization..." Biochem.Biophys.Res.Commun.198. 485-491 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sakai,N.et al.: "Puvfication and characteuization...." J.Biochem. 116. 615-620 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tukamoto,H,et al.: "One base deletion in the cysteine rich..." Hum.Mole.Gernt.3. 995-996 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hayashi,J.et al.: "Functional and morphological..." J,Biol.Chem.269. 19060-19066 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yamamoto,T.et al.: "Bone mavon-derived o steoclast-lilce..." J.Clin.Iuvest.91. 362-367 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kawa-Ho.K.et al.: "Isolation of human herpesviws 7..." Br.J.Haematol.84. 545-548 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yanagihara,I.et al.: "Molecular and Cell Biology of Human Gere Therapeutics" Champman & Hall(in press),

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 乾: "Annual Revieu 内分泌・代謝、先天代謝異常199428HD02:1994" 中外医学社, 4

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sakai, N.et al.: "Krabbe disease : isolation and..." Biochem.Biophys.Res, Commun.198. 485-491 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sakai, N.et al.: "Punfication and characterization..." J.Biochem.116. 615-620 (1994)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1996-04-15  

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