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Immunoelectron microscopic analysis of basement membrane components in type VII collagen knockout skin

Research Project

Project/Area Number 12670836
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

ISHIKO Akira  Keio University School of Medicine, Dermatology, Assistant professor, 医学部, 専任講師 (10202988)

Co-Investigator(Kenkyū-buntansha) SHIMIZU Hiroshi  Hokkaido University School of Medicine, Dermatology, Professor, 医学部, 教授 (00146672)
SUZUKI Yosuke  Keio University School of Medicine, Dermatology, Researcher, 医学部, 助手 (90306845)
NISHIKAWA Takeji  Keio University School of Medicine, Dermatology,, Professor, 医学部, 教授 (50051579)
MASUNAGA Takuji  KOSE corporation Fundamental Research Laboratory, Chief researcher, 研究本部・基礎研究所, 研究員
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2001: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2000: ¥1,600,000 (Direct Cost: ¥1,600,000)
Keywordstype VII collagen / epidermolysis bullosa / immunoelectron microscopy / BPAG2 / laminin 5 / basement membrane / mutation analysis
Research Abstract

Receive dystrophic epidermolysis bullosa (RDEB) is a congenital bullous disease caused by lack of type VII collagen that anchors epidermal basement membrane (lamina densa) to the dermis. Molecular relationship between the type VII collagen and the other epidermal basement membrane molecules is not fully elucidated. The purpose of this study is to elucidate the in vivo molecular ultrastructural relationship between the type VII collagen and the other basement membrane molecules using the skin of RDEB patients, which were the type VII knockout human skin. For this, the precise ultrastructural localization of basement membrane molecules including type VII collagen, BPAG2, laminin 5 were compared between the type VII collagen knockout human skin and the normal human skin. The diagnosis of RDEB confirmed by electron microscopy and the lack of expression of LH7.2 antigen, N-terminus domain of type VII collagen. Blood samples from the five patients with RDEB were processed for genomic DNA elution. COL7A1 gene that encodes type VII collagen was amplified and DNA sequences were analyzed. Among ten alleles, three mutations on four alleles were identified: 6573+1G>C, 5504delA and 5818delC. Skin samples were obtained from three RDEB patients by consent. Localizations of N and C terminus of BPAG2, and laminin 5 were observed with post-embedding immunogold electron microscopy and compared statistically with those of normal human skin. As results, the N terminus of BPAG2 was localized at the hemidesmosome and laminin 5 was localized at lamina densa. There was no significant difference in localization of these molecules between normal and RDEB skin. However, C-terminus of BPAG2 were significantly shifted from lamina densa to the epidermal side. These results indicated that type VII collagen may have some molecular interaction between BPAG2 via C-terminal domain of BPAG2, both of which were localized at lamina densa in the normal skin.

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Yasuko Takizawa., et al.: "Compound heterozygosity for a point mutation and a deletion located at slice acceptor sited I the LAMB3 gene leads to generalized atrophic benign epidermolysis bullosa"J Invest Dermatol:, 2000. 115. 312-316 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Detlef Zillikens., et al.: "Autoantibodies in anti-p200 pemphigoid stain skin lacking laminin 5 and type VII collagen"Br J Dermatol. 143. 1043-1045 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shuko Nonaka., et al.: "The extracellular domain of BPAG2 has a loop structure on the carboxy terminal flexible tail in vivo"J Invest Dermatol. 115. 889-892 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Takayuki Murata., et al.: "Glycine substitution mutations by different amino acids in the same codon of DOL7A1 lead to heterogeneous clinical phenotypes of dominant dystrophic epidermolvsis byllosa"Arh Dermtaol Res. 292. 477-481 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Akira Ishiko, Hiroshi Shimizu: "Electron microscopy in diagnosis of autoimmune bullous disorders"Clinics in Dermatology. 19. 631-637 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 石河 晃: "皮膚基底膜部の組織構築と疾患"組織培養工学. 26. 217-221 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yasuko Takizawa, Yoshiki Hiraoka, Hayato Takahashi, Akira Ishiko, Isamu Yasuraoka, Isao Hashimoto, Sadakazu Also Takeji Nishikawa, Hiroshi Shimizu: "Compound heterozygosity for a point mutation and a deletion located at slice acceptor sited I the LAMB3 gene leads to generalized atrophic benign epidermolysis bullosa"J Invest Dermatol. 115. 312-316 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Detlef Zillikens, Akira Ishiko, Marcel F. Jonkman, lakov Chimanovich, Hiroshi Shimizu, Takashi Hashimoto, and Eva-B. Brocker: "Autoantibodies in anti-p200 pemphigoid stain skin lacking laminin 5 and type VII collagen"Br J Dermatol. 143. 1043-1049 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shuko Nonaka, Akira Ishiko, Takuji Masunaga, Masashi Akiyama, Katsushi Owaribe, Hiroshi Shimizu and Takeji Nishikawa: "The extracellular domain of BPAG2 has a loop structure on the carboxy terminal flexible tail in vivo"J Invest Dermatol. 115. 889-892 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Takayuki Murata, Takuji Masunaga, Hiroshi Shimizu, Yasuko Takizawa, Akira Ishiko, Naohito Hatta, Takeji Nishikawa: "Glycine substitution mutations by different amino acids in the same codon of DOL7A1 lead to heterogeneous clinical phenotypes of dominant dystrophic epidermolysis byllosa"Arh Dermtaol Res. 292. 477-481 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Akira Ishiko and Hiroshi Shimizu: "Electron microscopy in diagnosis of autoimmune bullous disorders"Clinics in Dermatology. 19. 631-637 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Akira Ishiko, Hiroshi Shimizu: "Electron microscopy in diagnosis of autoimmune bullous disorders"Clinics in Dermatology. 19. 631-637 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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