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Gene therapy for epidermolysis bullosa using cultured keratinocytes sheet

Research Project

Project/Area Number 09470192
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Dermatology
Research InstitutionKeio University

Principal Investigator

SHIMIZU Hiroshi  Keio University School of Medicine, Department of Dermatology, Associate Professor, 医学部, 助教授 (00146672)

Co-Investigator(Kenkyū-buntansha) NISHIKAWA Takeji  Keio University School of Medicine, Department of Dermatology, Professor, 医学部, 教授 (50051579)
AMAGAI Masayuki  Keio University School of Medicine, Department of Dermatology, Assistant Profess, 医学部, 講師 (90212563)
TANAKA Masaru  Keio University School of Medicine, Department of Dermatology, Assistant Profess, 医学部, 講師 (40188339)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥13,100,000 (Direct Cost: ¥13,100,000)
Fiscal Year 1998: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 1997: ¥10,200,000 (Direct Cost: ¥10,200,000)
Keywordsepidermolysis bullosa / laminin 5 / type VII collagen / gene therapy / epidermis / keratinocyte / gene transfection / basement membrane / Vil型コラーゲン / 培養表皮シート / 遺伝子導入 / 劣性栄養障害型 / Herlitz致死型 / laminin5 / SV40
Research Abstract

In this study, we have tried to establish the treatment system for epidermolysis bullosa using keratinocyte cell culture sheet and gene transfection. Herlitz junctional epidermolysis bullosa (H-JEB) is a lethal subtype of epidermolysis bullosa in which a complete deficiency of laminin 5. Laminin 5, a component of epidermal basement membrane, is composed of alpha3, beta3 and gamma2 polypeptide chains encoded b y LAMA3, LAMB3 and LAMC2 gene, respectively. Laminin 5 molecule is first synthesized in the basal keratinocytes as individual monomer, followed by glycosylation. Thereafter, beta3 and gamma2 chains assemble into a heterodimer, beta3gamma2, followed by incorporation of the alpha3 chain to form a heterotrimer, alpha3beta3gamma2. Only the assembled heterotrimer is secreted and processed by proteolytic enzyme to form the mature laminin 5 molecule. The complete deficiency of laminin 5 molecule due to gene mutation is known to result in a lethal type of autosomal recessive skin blistering disorder, Herlitz junctional epidermolysis bullosa (H-JEB). In this study, we showed the clinical and immunohistochemical features of this patient, and established the SV4O-transformed keratinocyte cell line, in which re-expression of beta3 chain of laminin 5 was confirmed by transfection with wild type LAMB3 cDNA.

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] Shimizu H et al: "Saccessful prenatal exclusions of anspecified subtypes of severe epidermolysis bullosa" Int J Dermatol. 37. 364-369 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shimizu H et al: "The 97 KDa linear Ig A ballous dermatosis untiger is not expressed in a patient with generalized atrophic benign epidermolysis ballosa with a novel homozygous G258X mutation incoL17AI." J Invest Dermatol. 111. 887-892 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shimizu H et al: "Immunchistochemical, ultrastrustural and molecular features of Kindlersyndrome distinguish it from dystrophic epidermolysis bictfosa" Arch Dermatol. 133. 1111-1117 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shimizu H et al: "Most anchoring fibrils in human skin originate and terminate in the laminadense" Lab Invest. 76. 753-763 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takizawa Y Shimizu H et al: "Combination of a novel fromeshift mutation (1929 delCA) and a recurrent nonsense mutation (W610X) of the LAMB3 gene in a Japanese patient with Heriifz junctional epidermolysis bullosa. and their application for prenatal testing" J Invest Dermatol. 111. 1239-1241 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takizawa Y Shimizu H et al: "Novel premature termination codon mutations in the laminin γ2-chain gene (LAMC2) in Herlitz junctional epidermolysis bullosa" J Invest Dermatol. 111. 1233-1234 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takizawa Y,Shimizu H,Rouan F,Kawai M,Udono M,Pulkkinen L,Nishikawa T,Uitto J: "Four novel plectin gene mutations in Japanese patients with epidermolysis bullosa with muscular dystrophy." J Invest Dermatol. 112. 109-112 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takizawa Y,Shimizu H,Pulkkinen L,Suzumori K,Kakinuma H,Uitto J,Nishikawa T: "Combination of a novel frameshift mutation (1929delCA) and a recurrent nonsense mutation (W610X) of the LAMB3 gene in a Japanese patient with Herlitz junctional epidermolysis bullosa, and their application for prenatal testing." J Invest Dermatol. 111. 1239-1241 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ishiko A,Shimizu H,Masunaga T,Yancey KB,Giudice G,Zone JJ,Nishikawa T: "97kDa linear IgA bullous dermatosis antigen localizes in the lamina lucida between NC16A domain and carboxyl terminal domains of the 180 kDa bullous pemphigoid antigen." J Invest Dermatol. 111. 93-96 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takizawa Y,Shimizu H,Pulkkinen L,Nonaka S,Nishikawa T,Uitto J: "Novel premature termination codon mutations in the laminin _<gamma2>2-chain gene (LAMC2) in Herlitz junctional epidermolysis bullosa." J Invest Dermatol. 111. 1233-1234 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takizawa Y,Pulkkinen L,Shimizu H,Lin L,Hagiwara S,Nishikawa T,Uitto J: "Maternal uniparental meroisodisomy in the LAMB3 region of chromosome 1 results in lethal junctional epidermolysis bullosa." J Invest Dermatol. 110. 828-831 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shimizu H,Horiguchi Y,Suzumori K,Watanabe I,Owaribe K,Nishikawa T: "Successful prenatal exclusions of an unspecified subtypes of severe epidermolysis bullosa." Int J Dermatol. 37. 364-369 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takizawa Y,Shimizu H,Pulkkinen L,Hiraoka Y,McGrath JA,Suzumori K,Aiso S,Uitto J,Nishikawa T: "Novel mutations in the LAMB3 gene shared by two Japanese unrelated families with Herlitz junctional epidermolysis bullosa, and their application for prenatal testing." J Invest Dermatol. 110. 174-178 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shimizu H,Takizawa Y,Pulkkinen L,Zone JJ,Matsumoto K,Saida T,Uitto J,Nishikawa T: "The 97kDa linear IgA bullous dermatosis antigen is not expressed in a patient with generalized atrophic benign epidermolysis bullosa with a novel homozygous G258X mutation in COL17A1." J Invest Dermatol. 111. 887-892 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shimizu H,Sato M,Ban M,Kitajima Y,Ishizaki S,Harada T,Bruckner-Tuderman L,Fine J-D,Burgeson R,Kon A,McGrath JA,Christiano AM,Uitto J,Nishikawa T: "Immunohistochemical, ultrastructural and molecular features of Kindler syndrome distinguish it from dystrophic epidermolysis bullosa." Arch Dermatol. 133. 1111-1117 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shimizu H,Ishiko A,Masunaga T,Kurihara Y,Sato M,Bruckner-Tuderman L,Nishikawa T: "Most anchoring fibrils in human skin originate and terminate in the lamina densa." Lab Invest. 76. 753-763 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takizawa Y Shimizu H et al: "Novel mutations in the LAMB3 gene shared by the Japanese unrelared families with Herlith junctional epidermolysis buiiosa,and their application for prenatal testing" J Invest Dermatol. 110. 174-178 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Takizawa Y Shimizu H et al: "Maternal uniparental meroisodisomy in the LAMB3 region of chromosome 1 results in lethal junctional epidermolysis bullosa." J Invest Dermatol. 110. 828-831 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Shimizu H et al: "Successful prenatal exclusions of an unspecified subtypes of severe epidermolysis ballosa" Int J Dermatol. 37. 364-369 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Shimizu H et al: "The 97-KD linear IgA bullous dermatosis antigen is not expressed in a patient with generalized atrophic henigh epidermolysis bullosa with a novel homozygous G258X mutation in COL17A1" J Invest Dermatol. (in press).

    • Related Report
      1998 Annual Research Report
  • [Publications] Takizawa Y Shimizu H et al: "Novel premature termination coder mutations in the laminin 92-chain gene (LAMC2)in Herlitz junctional epidermolysis bullosa" J Invest Dermatol. (in press).

    • Related Report
      1998 Annual Research Report
  • [Publications] Takizawa Y Shimizu H et al: "Combination of a novel frameshift mutation(1929delCA)and a recarrent nansense mutation(W610X)of the LAMB3 gene in Japanese patient with Herlitz junctional epidermolysis bullosa" J Invest Dermatol. (in press).

    • Related Report
      1998 Annual Research Report
  • [Publications] Shimizu Hiroshi et al.: "Most Anchoring Fibrils in Human Skin Originate and Terminate in the Lamina Densa" LABORATORY INVESTIGATION. 76・6. 753-763 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Shimizu Hiroshi et al.: "Immunohistochemical,Ultrastructural,and Molecular Features of Kindler Syndrome Distinguish It From Dystrophic Epidermolysis Bullosa" ARCH DERMATOL. 133. 1111-1117 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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