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Basic Research for Gene Therapy of Congenital Hyperbilirubinemia

Research Project

Project/Area Number 08670878
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionShiga University of Medical Science

Principal Investigator

SATO Hiroshi  Shiga University of Medical Science, Medical School Biology Associate Professor, 医学部, 助教授 (90090430)

Co-Investigator(Kenkyū-buntansha) 山本 和雄  滋賀医科大学, 医学部, 医員
Project Period (FY) 1996 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1997: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1996: ¥900,000 (Direct Cost: ¥900,000)
KeywordsCongenital Hyperbilirubinemia / UGT1A1 / Bilirubin / UDP-Glycosyltransferase / Crigler-Najiar Syndrome / Gene Therapy / 黄疸 / 遺伝子 / ギルバ-ト症候群
Research Abstract

There has been no sufficient data for the expression of bilirubin UDP-glycosyltransfearse gene (UGT1A). So, we fist tried to clarify the regulation of the UGT1A1 expression as a first step of gene therapy, and we analyzed the promoter region (up to-3190) of UGT1A1 by transient transfection assay to identify transcriptionally regulatory sequences and found two elements ; one was between-1362 and-1220 and the other between-113 and-70. The proximal one (PE) consisted of two elements, E-box (-104 to-95) and HNF-1 site (-91 to-79). Distal element had sequences similar to those of AP-1 and CREB,but we could not demonstrate the bindings of the factors to DE by gel mobility-shift assay.

Report

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

    (35 results)

All Other

All Publications (35 results)

  • [Publications] Koiwai, O.: "Crigler-Najjar syndrome type II is inherited both as a dominant and as a recessive trait." 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] Sato, H.: "The genetic basis of Gilbert's syndrome." Lancet. 347. 556-557 (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 background of constitutional unconjugated hyperbilirubinemia." Int Hepatol Commun. 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] 佐藤 浩: "遺伝子黄疸-Crigler-Najjar症候群とGilbert症候群の遺伝子解析-" Porphyrins. 5. 177-184 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kamisako, T.: "Mutiplicity of mutation in UDP-glucuronosylktransferase 1^* gene in Gilbert's syndrome." Int.Hepatol.Commun.6. 249-252 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 添田 陽子: "Gilbert症候群患者におけるビリルビンUDP-グルクロン酸転移酵素遺伝子のTATA boxとコード領域の解析" 滋賀医科大学雑誌. 12. 61-70 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 足立 幸彦: "体質性黄疸の分子生物学的研究の進歩" 日本内科学雑誌. 86. 1467-1469 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 上硲 俊法: "体質性黄疸の病態と遺伝的背景" 最新医学. 52. 532-542 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Maruo, Y.: "Gilbert's syndrome due to a homozygous mis-sense mutation (Tyr486Asp)of bilirubin UDP-glycuronosyltransferase gene." J.Pediat.(in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yamamoto, K.: "Contribution of two missense mutations (G71R and Y486D)of the UGT1A1 gene to phenotypes of Gilbert's syndrome and Crigler-Najjar syndrome type II" Biochim.BIophys.Acta. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yamamoto, K.: "Mutation analysis of seven patients with Crigler-Najjar syndrome type II." J.Hum.Genet.(in press).

    • 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 bilirubin UDP-glyucuronosyl transferase gene (UGT1^*1)in relevance to Gilbert's syndrome." Hepatol.Res.(in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Koiwai O,Aono S,Adachi Y,Kamisako T,Yasui Y,Nishizawa M,Sato H: "Crigler-Najjar syndrome type II is inherited both as a dominant and as a 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] Sato H,Adachi Y,Koiwai O: "The genetic basis of Gilbert's syndrome." Lancet. 347. 557-8 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kamisako T,Soeda Y,Yamamoto K,Sato H,Adachi Y: "Mutiplicity of mutation in UDP-glucruonosyltransferase 1^<**>1 gene in Gilbert's syndrome." Int.Hepatol.Commun.6. 249-252 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yamamoto K,Soeda Y,Kamisako T,Hosaka H,Fukano M,Sato H,Fujiyama Y,Adachi Y,Satoh Y,Doida Y,Bamba T: Mutation analysis of seven patients with Crigler-Najjar syndrome type II.J.Hum Genet. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Ueyama H,Koiwai O,Soeda Y,Sato H,Satoh Y,Okubo I,Doida Y: "Analysis of the promoter of bilirubin UDP-glyucuronosyltransferase gene (UGT1^<**>1) in relevance to Gilbert's syndrome." Hepatol.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] Maruo Y,Sato H,Yamano T,Doida Y,Shimada M.: "Gilbert's syndrome due to a homozygous mis-sense mutation (Tyr486Asp) of bilirubin UDP-glycuronosyltransferase gene." J.Pediat.(in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yamamoto K,Sato H,Fujiyama Y,Doidab Y,Bamba T.: "Contribution of two missense mutations (Gly71Arg and Tyr486Asp) of the bilirubin UDP-glucuronosyltransferase gene to phenotypes of Gilbert's syndrome and Crigler-Najjar syndrome type II." Biochim.Biophys.Acta. (in press).

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

    • Related Report
      1997 Annual Research Report
  • [Publications] Sato,H.: "The genetic basis of Gilbert's syndrome." Lancet. 347. 556-557 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Adachi,Y.: "Genetic background of constitutional unconjugated hyperbilirubinemia." Int Hepatol Commun. 5. 297-307 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] 佐藤浩: "遺伝性黄疸-Crigler-Najjar症候群とGilbert症候群の遺伝子解析-" Porphyrins. 5. 177-184 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kamisako,T.: "Mutiplicity of mutation in UDP-glucuronosylktransferase 1^*1 gene in Gilbert's syndrome." Int.Hepatol.Commun.6. 249-252 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 添田陽子: "Gilbert症候群患者におけるビリルビンUDP-グルクロン酸転移酵素遺伝子のTATA boxとコード領域の解析." 滋賀医科大学雑誌. 12. 61-70 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 足立幸彦: "体質性黄疸の分子生物学的研究の進歩" 日本内科学雑誌. 86. 1467-1469 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 上硲俊法: "体質性黄疸の病態と遺伝的背景." 最新医学. 52. 532-542 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Maruo,Y.: "Gilbert's syndrome due to a homozygous mis-sense mutation (Tyr486Asp) of bilirubin UDP-glycuronosyltransferase gene." J.Pediat.(in press).

    • Related Report
      1997 Annual Research Report
  • [Publications] Yamamoto,K.: "Contribution of two missense mutations (G71R and Y486D) of the UGT1A1 gene to phenotypes of Gilbert's syndrome and Crigler-Najjar syndrome type II" Biochim.Biophys.Acta. (in press).

    • Related Report
      1997 Annual Research Report
  • [Publications] Yamamoto,K.: "Mutation analysis of seven patlents with Crigler-Najjar syndrome type II" J.Hum.Genet.(in press).

    • Related Report
      1997 Annual Research Report
  • [Publications] Ueyama,H.: "Analysis of the promoter of bilirubin UDP-glyucuronosyl transferase gene (UGT1^*1) in relevance to Gilbert's syndrome." Hepatol.Res.(in press).

    • Related Report
      1997 Annual Research Report
  • [Publications] Sato H,Adachi Y,Koiwai O: "The genetic basis of Gilbert's syndrome." Lancet. 347. 557-558 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Koiwai O,Aono S,Adachi Y,Kamisako T,Yasui Y,Nishizawa M,Sato H: "Crigler-Najjar syndrome type II is inherited both as a dominant and as a recessive trait." Hum Mol Genet. 5. 645-647 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Adachi Y,KAmisako T,Koiwai O,Yamamoto K,Sato H: "Genetic background of constitutional unconjugated hyperbilirubinemia." Int.Hepatol.Commun.5. 297-307 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 佐藤浩、添田陽子、佐藤譲、土井田幸郎: "遺伝子黄疸-Crigler-Najjar症候群とGilbert症候群-の遺伝子解析" ポルフィリン. 5. 177-184 (1996)

    • Related Report
      1996 Annual Research Report

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

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