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Gene analysis and gene therapy in tyrosinemias.

Research Project

Project/Area Number 05671886
Research Category

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

Allocation TypeSingle-year Grants
Research Field Human genetics
Research InstitutionKumamoto University

Principal Investigator

ENDO Fumio  Department of Hospital Lecturer, 医学部・附属病院, 講師 (00176801)

Project Period (FY) 1993 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1994: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1993: ¥1,200,000 (Direct Cost: ¥1,200,000)
Keywordstyrosinemia / gene mutation / gene structure / animal model / recombinant adenovirus / gene therapy / チロジン / 遺伝子 / 突然変異 / モデルマウス / HPD
Research Abstract

We have clone cDNA for human, mouse and porcine 4-hydroxyphenylpyruvate dioxygenase from cDNA libralies constructed from mRNA of human, mouse and porcine liver respectively, Using human and mouse cDNA as proves, we obstained DNA fragments containing exons of HPD from human and mouse genomic libraries, Through these studies we have clarified the structure of human and mouse HPD gene. Similarly, we have elucidated the structures of cDNA and gene for human fumarylacetoacetase.
Based on these progress we analyzed gene mutations in human FAH gene from a Japanese patient with type 1 tyrosinemia and mouse HPD gene from III mouse, a tyrosinemic mouse.These studies revealed mutations on FAH gene and HPD gene, respectively.
Using abino lethal mouse which is defective for Fah, and III mouse which is defective for HPD,we generated mice which carry both mutation, one on FAH gene and one on HPD gene. Fah deficient mice were neonatally lethal but these double mutants were vaiable, indicating that defective HPD gene rescues the lethal phenotype of albino deletion mouse.
Futher, we constructed recombinant adenovirus which express human HPD.In cultured cells, transduction of the recombinant virus effectively expresses human HPD.This recombinant virus will be useful to express human HPD in experimental animals.

Report

(3 results)
  • 1994 Annual Research Report   Final Research Report Summary
  • 1993 Annual Research Report
  • Research Products

    (21 results)

All Other

All Publications (21 results)

  • [Publications] Endo F.,et al.: "Measurement of blood holoceruloplasmin by El α using a mouse monoclonal antibody directed to holoceruloplasmin.Implicatin for mass screening of Wilson disease." J.Inher.Metab.Dis.17. 616-620 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Endo F.,et al.: "Structure of he human 4-hydroxyphenylpyruvic acid dioxygenase(HPD)" Genomics.23. 534-539 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Endo F.,et al.: "Characterization of a point mutation in the pyruvate El α gene from two boys with primary lactic acidemia." J.Inher.Metab.Dis.17. 189-195 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Endo F.,et al.: "Structtural organization and analysis of human fumarylacetoacetate hydrolase gene in tyrosinemia type I." Biochem,Biophys.Acta.1226. 168-172 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Endo F.,et al.: "A nonsense mutation in the 4-hydroxyphenylpyuvic acid dioxugenase causes skipping of the constitutive exon and hypertyrosinemia in mouse strain III." Genomics.25. 164-169 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Endo F.,et al.: "Exess copper and ceruloplasmin biosynthesis in long-term cultured hepatocytes from Long-Evans Cinnamon(LEC)rats,a model of Wilson disease." J.Biol.Chem.(in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Endo F., et al.: "Measurement of blood holoceruloplasmin by E_1 alpha using a mouse monoclonal antibody directed to holoceruloplasmin. Implication for mass screening of Wilson disease." J.Inher.Metab.Dis.17. 616-620 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Endo F., et al.: "Structure of he human 4-hydroxyphenylpyruvic acid dioxygenase (HPD)" Genomics. 23. 534-539 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Endo F., et al.: "Chracterization of a point mutation in the pyruvate E_1alpha gene from two boys with primary lactic acidemia." J.Inher.Metab.Dis.17. 189-195 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Endo F., et al.: "Structural organization and analysis of human fumarylacetoacetate hydrolase gene in tyrosinemia type 1." Biochem.Biophys.Acta.1226. 168-172 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Endo F., et al.: "A nonsense mutation in the 40hydroxyphenylpyuvic acid dioxugenase causes skipping of the constitutive exon and hypertyrosinemia in mouse strain III" Genomics.25. 164-169 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Endo F., et al.: "Exess copper and ceruloplasmin biosynthesis in long-term cultured hepatocytes from Long-Ecans Cinnamon (LEC) ras, a model of Wilson disease" J.Biol.Chem. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Endo F.,et al.: "Measurement of blood holoceruloplasmin by E1 α using a mouse monoclonal antibody directed to holoceruloplasmin. Implicatin for mass screening of Wilson disease." J.Inher.Metab.Dis.17. 616-620 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Endo F.,et al.: "Structure of he human 4-hydroxyphenylpyruvic acid dioxygenase(HPD)" Genomics.23. 534-539 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Endo F.,et al.: "Characterization of a point mutation in the pyruvate E1 α gene from two boys with primary lactic acidemia." J.Inher.Metab.Dis.17. 189-195 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Endo F.,et al.: "Structural organization and analysis of human fumarylacetoacetate hydrolase gene in tyrosinemia type I." Biochem,Biophys.Acta.1226. 168-172 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Endo F.,et al.: "A nonsense mutation in the 4-hydroxyphenylpyuvic acid dioxgenase causes skipping of the constitutive exon and hypertyrosinemia in mouse strain III." Genomics.25. 164-169 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Endo F.,et al.: "Exess copper and ceruloplasmin biosynthesis in long-term cultured hepatocytes from Long-Evans Cinnamon(LEC)rats,a model of Wilson disease." J.Biol.Chem.(in press).

    • Related Report
      1994 Annual Research Report
  • [Publications] Endo F.,et al.: "Structural organization of human fumarylace to acetate hydrolase gene and gene analysis in tvrosinemia type 1." Biochem.Biophy.Acta. (in press).

    • Related Report
      1993 Annual Research Report
  • [Publications] 遠藤文夫 他: "遺伝性高チロジン血症マウスにおける遺伝子異常" 日本先天性代謝異常学会雑誌. 9. 153 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 遠藤文夫 他: "遺伝性高チロジン血症マウス" 最新医学. 48. 1554-1559 (1993)

    • Related Report
      1993 Annual Research Report

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Published: 1993-04-01   Modified: 2016-04-21  

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