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Gene therapy for Crigler-Najjar syndrome type l by using a model animal

Research Project

Project/Area Number 08671202
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 内分泌・代謝学
Research InstitutionSCIENCE UNIVERSITY OF TOKYO,Faculty of Science & Technology (1997)
Aichi Cancer Center Research Institute (1996)

Principal Investigator

KOIWAI Osamu  Science University of Tokyo Dep.of Applied Biological Science Asistant prof., 理工・応用生物, 助教授 (50132923)

Co-Investigator(Kenkyū-buntansha) AONO Sachiko  Aichi Prefectural Colony Chief.Researcher, 発達障害研究所・周生期, 主任研究員 (20231780)
Project Period (FY) 1996 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1997: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1996: ¥1,600,000 (Direct Cost: ¥1,600,000)
KeywordsGene therapy / Jaundice / Bilirubin / Glucuronic acid / Baculovirus / Liver / Gene expression / グルクロン酸転移酵素 / クリグラーナジャー症候群 / がんラット
Research Abstract

Crigler-Najjar syndrome typel is a hereditary disease which is caused by the defect of bilirubin UDP-glucuronosyl transferase (UDPGT) gene. We have tried the gene therapy for the Crigler-Najjar syndrome typel using a model animal, Gunn rat. Recently, it was reported that Baclrovirus specifically infects human liver cells. To apply the baculovirus system to the gene therapy, we firstly constructed the expression vector of bilirubin UDPGT cDNA and transfected to Sf9 insectcells.We could detect the bilirubin UDPGT band expressed in Sf9 cells by Western blotting. We cloud also detect high bilirubin UDPGT activity by the method of thin layr chromatography. Next we constructed a expression vector having alpha1-antitrypsin promoter which specifically works in liver cells. Now we are transfecting the expression vector to HepG2 or Huh7 cells to conferm the availability of the vector in liver cells. We have analyzed the promoter region by constructing thedeletion series of the region in detail. We clarified that HNF-1 and APS elements are essential to the expression of the bilirubin UDPGT gene.

Report

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

    (19 results)

All Other

All Publications (19 results)

  • [Publications] Soeda, Y: "A predicted homozygous case of missensemutaion in Gilbent's syndrome" Lancet. 346. 1494 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Koiwai, O: "Criglar-Najjar Syndrome type II is inherited both as a dominant and as a" Hum.Mol.Genet.5. 645-647 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Adachi, Y: "Genetic back ground of constitutional unconjugated hyperb" Intern.Hep.Com.5. 297-307 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Sato, H: "Progress in determining the genetic basis of Gilbert's syn" Lancet. 347. 557-558 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Ueyama, H: "Analysis of the promoter of human bilirubin UDP-glucu" Hepatology Res.(in press). (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Soeda, Y., Tamamoto, K., Adachi, Y., Hayashi, K., Aono, S., Koiwai, O.and Sato, H.: "A predicted homozygous case of missense mutation in Gilbert's syndrome" Lancet. 346. 1494 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Koiwai, O., Aono, S., Adachi, Y., Kamisako, T., Yasui, Y., Nishizawa, M.and Sato, H.: "Crigler-Najjar syndrome type II is inherited both as a dominant and as recessive trait" Hum.Mol.Genet.5. 645-647 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Adachi, y., Kamisak, T., Koiwai, O., Yamamoto, K.and Sato, H: "Genetic back ground of constitutional unconjugated hyperbilirubinemia." Intern.Hep.Com.5. 297-307 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] H.Sato, Y.Adachi and O.Koiwai: "Progress in determining the genetic basis of Gilbert's syndrome" Lancet. 347. 557-558 (1966)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] H.Ueyama, O.Koiwai, Y.Soeda, H.Sato, Y.Satoh, I.Ohkubo and Y.Doida: "Analysis of the promoter of human bilirubin UDP-glucuronosyl transferase gene (UGT ^*1) in relevance to Gibert's syndrome" Hepatology Res.(in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Soeda,Y: "Apredicted homozygous case of misseuse mutation in Gilbert's synd" Lancet. 346. 1494 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Koiwai,O: "Crigler-Najjan Syndrome TypeII is inherited both as a dominant and" Hum.Mol.Genet.5. 645-647 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Adachi,O: "Genetic back ground of constitutional uncoijugated byperbi" intern.Hep.Com.5. 297-307 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Sato.H: "Progress in determining the genetic basis of Gilbert's syndro" Lancet. 347. 557-558 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ueyama,H: "Analysis of the promoter of human bilirubin UDP-glucuron" Hepatology Res.(in Press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Y.Soeda: "A predicted homozygous case of missense mutation in Gilbert's syndrome." Lancet. 346. 1494- (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] O.Koiwai: "Criglar Najjar syndrome TypeII is inherited both as a dominaut and as a ressesive trait." Human Molecular Genetics. 5. 645-647 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] H.Sato: "Progress in determining the genetic basis of Gilbert's syndrome" Lancet. 347. 557-558 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Y.Adachi: "Genetic back ground of constitutional unconjugated hyperbilirubinemia" International Hepatology Communications. 5. 297-307 (1996)

    • Related Report
      1996 Annual Research Report

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

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