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Functional expression of Wilson's disease gene in the LEC rats by adenovirus-mediated gene delivery.

Research Project

Project/Area Number 08670134
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General medical chemistry
Research InstitutionAkita University

Principal Investigator

TERADA Kunihiko  Akita University School of Medicine, Assistant Prof., 医学部, 講師 (60197796)

Co-Investigator(Kenkyū-buntansha) SUGIYAMA Toshihiro  Akita University School of Medicine, Prof., 医学部, 教授 (00127242)
Project Period (FY) 1996 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1997: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1996: ¥1,400,000 (Direct Cost: ¥1,400,000)
KeywordsAdenoviral vector / Gene therapy / Wilson's disease / LEC rats / Golgi apparatus / Ceruloplasmin / Copper transporting P-type ATPase / 銅輸送P型 ATPase / P-type ATPase / 組換えアデノウィルス
Research Abstract

WND gene (officially designated ATP7B), which encodes a putative copper transporting P-type ATPase, is defective in the patients with Wilson's disease, resulting in the excessive accumulation of copper in the liver. The Long-Evans Cinnamon (LEC) rat, known as a rodent model for Wilson's disease, shows some of clinical features similar to Wilson's disease. Atp7b, the rat gene homologue to WND,is also defective in the rat. To investigate the in vivo function of WND protein as well as its intracellular localization, WND cDNA was introduced to the LEC rats by recombinant adenovirus mediated gene delivery. The recombinant adenoviruses containing WND cDNA,1X10^<10> plaque forming units, were administered to 4-6 week old LEC rats by tail vein injection. Immunofluorescent study and subcellular fractionation study revealed the transgene expression in liver and its localization to the Golgi apparatus. Moreover, since the synthesis of holoceruloplasmin is disturbed in the LEC rat, the plasma level of holoceruloplasmin, oxidase active and copper bound form, was examined to evaluate the function of WND protein with respect to the copper transport. Consequently, the appearance of holoceruloplasmin in plasma was confirmed by Western blot analysis and plasma measurements for the oxidase activity and the copper content. Conclusions : 1) Introduced WND protein may function in the copper transport coupled with the synthesis of ceruloplasmin. 2) The Golgi apparatus is the likely site for WND protein to manifest its function. 3) Adenovirus mediated gene delivery could be a possible treatment for Wilson's disease.

Report

(3 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • Research Products

    (18 results)

All Other

All Publications (18 results)

  • [Publications] Terada K et al.: "Restoration of holoeruloplasmin synthesis LEC rat after infusion of recombinant adenovirus bearing WND cDNA." J.Biol.Chem.273. 1815-1820 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yang X-L et al.: "Two forms of Wilson disease proteins produced by slternative splicing are localized in distinct celluar compartment." Biochem.J. 326. 897-902 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Suzuki H et al.: "Gene amplifiction of int-2 and erbB in human esophageal cancer:relationship to clinocopatholgical varibles." Cancer Invest.15. 411-415 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kuhara M et al.: "Enhancing effect of a congenital disorder in methionine methionine metabolism on the development of spontaneous hepatoma in LEC rats." J.Trace Elem.Exp.Med.10. 61-71 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yasui O et al.: "Isolation of val cells from Long-Evans Cinnamon rats and their transformation into hepatocytes in vivo in the rat liver." Hepatology. 25. 329-334 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 杉山 俊博、他: "Wilson病とトランスポータ" 最新医学. 51. 71-76 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Terada K et al.: "Restoration of holoceruloplasmin synthesis in LEC rat after infusion of recombinant adenovirus bearing WND cDNA" J.Biol.Chem.273. 1815-1820 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yang X-L et al.: "Two forms of Wilson disease proteins produced by alternative splicing are localized in distinct cellular compartment." Biochem.J.326. 897-902 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Suzuki H et al.: "Gene amplification of int-2 and erbB in human esophageal cancer : relationship to clinicopathological variables." Cancer Invest.15. 411-415 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kuhara M et al.: "Enhancing effect of a congenital disorder in methionine metabolism on the development of spontaneous hepatitis and hepatoma in LEC rats." J.Trace Elem.Exp.Med.10. 61-71 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yasui O et al.: "Isolation of oval cells from Long-Evans Cinnamon rats and their transformation into hepatocytes in vivo in the liver." Hepatology. 25. 329-334 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Sugiyama T et al.: "Wilson disease and copper transporter." Saishin-igaku (Japanese). 51. 71-76 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Terada K et al.: "Restoration of holoceruloplasmin synthesis in LEC rat after infusion of recombinant adenovirus bearing WND cDNA" J.Biol.Chem.273. 1815-1820 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Suzuki H et al.: "Gene amplification of int-2 and erbB in human esophageal cancer:relationship to clinocopathological variables." Cancer Invest.15. 411-415 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yang X-L et al.: "Two forms of Wilson disease proteins produced by alternative splicing are localized in distinct cellular compartment." Biochem.J.326. 897-902 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kuhara M et al.: "Enhancing effect of a congenital disorder in methionine metabolism on the development of spontaneous hepatitis and hepatoma in LEC rats." J.Trace Elem.Exp.Med.10. 61-71 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yasui O et al.: "Isolation of oval cells from Long-Evans Cinnamon rats and their transformation into hepatocytes in vivo in the rat liver." Hepatology. 25. 329-334 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yasui,O.et.al.: "Isolation of oval cells from Long-Evans Cinnamon rats and their transformation into hepatocytes in vivo in the rat liver" Hepatology. 25. 329-334 (1997)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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