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Development of knockout mouse of desmoyokin(AHNAK)and analysis of its functio

Research Project

Project/Area Number 11470186
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Dermatology
Research InstitutionKurume University School of Medicine(Department of Dermatology)

Principal Investigator

MORI Osamu  Kurume University School of Medicine, Dermatology, Professor, 医学部, 教授 (20129597)

Co-Investigator(Kenkyū-buntansha) NAKAMA Takekuni  Kurume University School of Medicine, Dermatology, Associated Professor, 医学部, 講師 (50221453)
KUSUHARA Masahiro  Kurume University School of Medicine, Dermatology, Associated Professor, 医学部, 講師 (40195441)
MORI Osamu  Kurume University School of Medicine, Dermatology, Associated Professor, 医学部, 助教授 (10175630)
ITO Kyogo  Kurume University School of Medicine, Immunology, Professor, 医学部, 教授 (50125499)
橋本 隆  久留米大学, 医学部, 教授 (20129597)
目加田 英輔  久留米大学, 分子生命科学研究所, 教授 (20135742)
山田 源  熊本大学, 動物資源開発技術開発部門, 教授 (80174712)
Project Period (FY) 1999 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥12,300,000 (Direct Cost: ¥12,300,000)
Fiscal Year 2001: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 1999: ¥4,600,000 (Direct Cost: ¥4,600,000)
KeywordsDesmosome / Knockoit mouse / Desincykin / AHNAK / Keratinocyte / BS cell / Cell adhesion / molecular biclogy / デスモソーム / 核移行 / 細胞膜 / デスモヨーキンケラチノサイト / デスモグレイン / エンボプラキン
Research Abstract

In the present study, in order to clarify the role of the molecule (desmoyokin/AHNAK protein), we successfully established gene targetting mice (knockout mice) of desmoyokin/AHNAK protein. We screened mouse genomic DNA from mouse genomic DNA library, and prepared a targetting vector for desmoyokin/AHNAK protein. We inserted linealized targetting vector into enbryonic stem cells, and screened homologous recombinated cells. Using the homologous recombinated enbryonic stem cells, we prepare heterozygous mice and finally obtained homozygous knockout mice of desmoyokin/AHNAK protein. We have confirmed by both DNA and protein levels that these targetted mice are really lacking desmoyokin/AHNAK protein. At the same time, we also suceeded in preparation of desmoyokin/AHNAK protein knockout enbryonic stem cells, which should also be useful to examine the role of desmoyokin/AHNAK protein in the cell levels. We will examine the role of desmoyokin/AHNAK protein using these desmoyokin/AHNAK protein knockout mice and knockout enbryonic stem cells. These study should provide us with numerous important insights into the misterious giant protein, desmoyokin/AHNAK protein.

Report

(4 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • Research Products

    (44 results)

All Other

All Publications (44 results)

  • [Publications] Nousari HC, Deterding R, Wojtczack H, Aho S, Uitto J, Hashimoto T, Anhalt GJ: "The mechanism of respiratory failure in paraneoplastic pemphigus"N Eng J Med. 340. 1406-1410 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nie Z, Wang N, Amagai M, Hashimoto T: "C-terminus of Desmoyokin/AHNAK protein is mainly located in the nucleus in low calcium condition, but low to normal calcium shift translocates a part of it to cytoplasm"J Invest Dermatol. 114. 1044-1049 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] O'Toole EA, Mak LL, Guitart J, Woodley DT, Hashimoto T, Amagai M, Chan LS: "Induction of keratinocyte interleukin-8 expression and secretion by lgG autoantibodies as a novel mechanism of epidermal neutrophil recruitment in a pemphigus variant"Clin Exp Immunol. 119. 217-224 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nagata Y, Karashima T, Watt FM, Salmhofer W, Kanzaki T, Hashimoto T: "Paraneoplastic pemphigus sera react strongly with multiple epitopes on the various regions of envoplakin and periplakin, except for C-terminal homologous domain of periplakin"J Invest Dermatol. 116. 556-563 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Hashimoto T, Komai A, Futei Y, Nishikawa T, Amagai M: "Detection of IgA auoantibodies to desmogleins by an enzyme-lined immunosorbent assay -The presence of new minor subtypes of IgA pemphigus"Arch Dermatol. 137. 735-738 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Hamada T, Nagata Y, Tomita M Salmhofer W, Hashimoto T: "Bullous pemphigoid sera react specifically with various domains of BP230, most frequently with C-terminal domain, by immunoblot analyses using bacterial recombinant proteins covering entire molecule"Exp Dermatol. 10. 256-263 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Hashimoto T: "Clin Dermatol 19"Immunopathology of paraneoplastic pemhigus. 675-682 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nousari HC, Deterding R, Wojtczapk H, Aho S, Uitto J, Hashimoto T, Anhalt GJ: "The mechanism of respiratory failure in paraneoplastic pemphigus."N Eng J Med. 340. 1406-1410 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nie Z, Wang N, Amagai M, Hashimoto T: "C-terminus of Desmoyokin/AHNAK protein is mainly located in the nucleus in low calcium condition, but low to normal calcium shift translocates a part of it to cytoplasm."J Invest Dermatol. 114. 1044-1049 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] OToole EA, Mak LL, Guitart J, Woodley DT, Hashimoto T, Amagai M, Chan LS: "lnduction of keratinocyte interleukin-8 expression and secretion by IgG autoantibodies as a novel mechanism of epidermal neutrophil recruitment in a pemphigus variant."Clin Exp Immunol. 119. 217-224 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nagata Y, Karashima T, Watt FM, Salmhofer W, Kanzaki T, Hashimoto T: "Paraneoplastic pemphigus sera react strongly with multiple epitopes on the various regions of envoplakin and periplakin, except for C-termina! homologous domain of periplakin."J Invest Dermatol. 116. 556-563 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Hashimoto T, Komai A, Futei Y, Nishikawa T, Amagai M: "Detection of IgA auoantibodies to desmogleins by an enzyme-lined immunosorbent assay -The presence of new minor subtypes of IgA pemphigus."Arch Dermatol. 137. 735-738 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Hamada T, Nagaja Y, Tomita M, Salmhofer W, Hashimoto T: "Bullous pemphigoid sera react specifically with various domains of BP230, most frequently with C-terminal domain, by immunoblot analyses using bacterial recombinant proteins covering the entire molecule."Exp Dermatol. 10. 256-263 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nousari HC, Deterding R, Wojtczack H, Aho S, Uitto J, Hashimoto T: "Anhalt GJ : Themechanism of respiratory failure in paraneoplastic pemphigus"N Eng J Med. 340. 1406-1410 (1999)

    • Related Report
      2001 Annual Research Report
  • [Publications] Nie Z, Wang N, Amagai M, Hashimoto T: "C-terminus of Desmoyokin/AHNAK protein is mainly located in the nucleus in low calcium condition, but low to normal calcium shift translocates a part of it to cytoplasm"J Invest Dermatol. 114. 1044-1049 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] O'Toole EA, Mak LL, Guitart J, Woodley DT, Hashimoto T, Amagai M, Chan LS: "Induction of keratinocyte interleukin-8 expression and secretion by IgG autoantibodies as a novel mechanism of epidermal neutrophil recruitment in a, pemphigus variant"Clin Exp Immunol. 119. 217-224 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Nagata Y, Karashima T, Watt FM, Salmhofer W, Kanzaki T, Hashimoto T: "Paraneoplastic pemphigus sera react strongly with multiple epitopes on the various regions of envoplakin and periplakin, except for C-terminal homologous domain of, periplakin"J lnvest Dermatol. 116. 556-563 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hashimoto T, Komai A, Futei Y, Nishikawa T, Amagai M: "Detection of IgA autoantibodies to desmogleins by an enzyme-lined immunosorbent assay -The presence of new minor subtypes of IgA pemphigus"Arch Dermatol. 137. 735-738 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hamada T, Nagata Y, Tomita M, Salmhofer W, Hashimoto T.: "Bullous pemphigoid sera react specifically with various domains of BP230, most frequently with C-terminal domain, by immunoblot analyses using bacterial recombinant proteins covering the entire molecule"Exp Dermatol. 10(4). 256-263 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hashimoto T: "Clin Dermatol 19"Immunopathology of paraneoplastic pemphigus. 675-682 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Nie Z,Wang Nie,Amagai,Hashimoto T: "C-terminus of desmoyokin/AHNAK protein is mainly located in the nucleus in low Ca condition,but low to normal calcium shift translocates a part of it to cytoplasm"J Invest Dermatol. 114. 1044-1049 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Inoue M,Tamai K,Shimizu H,Nakama T,Hashimoto T et al: "A homozygous missense mutation in the cytoplasmic tail of b4 integrin,G931D, disrupts hemidesmosome assembly and underlies non-Herlitz junctional EB-"J Invest Dermatol. 114. 1061-1064 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ishii K,Amagai M,Ohata Y,Shimizu H,Hashimoto T et al: "Development of pemphigus vulgaris in a patient with pemphigus foliaceus : antidesmoglein antibody profile shift by enzyme-linked immunosorbent assay"J Am Acad Dermatol. 42. 859-861 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nie Z,Nagata Y,Joubeh S,Hirako Y,Owaribe K,Kitajima Y,Hashimoto T: "IgA antibodies of linear IgA bullous dermatosis recognize the 15th collagenous domain of BP180"J Invest Dermatol. 115. 1164-1166 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Pittella F,Katsube K,Kobayashi M,Takemura T,Kawano T,Hashimoto T et al: "Perinuclear and cytoplasmic distribution of desmoglein in esophageal squamous cell carcinomas"Pathology. in press.

    • Related Report
      2000 Annual Research Report
  • [Publications] Nagata Y,Karashima T,Watt FM,Kanzaki T,Hashimoto T: "PNP Sera React Strongly with Multiple Epitopes on the Various Regions of Envoplakin and Periplakin, Except for C-Terminal Homologous Domain of Periplakin"J Invest Dermatl. in press.

    • Related Report
      2000 Annual Research Report
  • [Publications] Komai A,Amgai M,Ishii K,T,Matsuo I,Hashimoto T et al: "The clinical transition between pemphigus foliaceus and pemphigus vulgaris correlates well with the changes in autoantibody profile assessed by an ELISA"Br J Dermatol. in press.

    • Related Report
      2000 Annual Research Report
  • [Publications] Hashimoto T,Komai A,Futei Y,Nishikawa T,Amagai M: "Desmogleins are targeted by IgA autoantibodies of a few IgA pemphigus patients"Arch Dermatol. in press.

    • Related Report
      2000 Annual Research Report
  • [Publications] 橋本隆: "「展望」自己免疫性水疱症-臨床でどこまで診断できるか"皮膚病診療. 22. 524-531 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 橋本隆: "水疱性疾患の分子生物学"医学のあゆみ. 195. 492-493 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 橋本隆: "皮膚疾患、特に自己免疫性水疱症と自己抗体"日本アフェレシス学会雑誌. 19. 154-160 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 橋本隆 ほか: "疱疹状天疱瘡の1例"臨床皮膚科. 54. 893-895 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 橋本隆: "皮膚科専門医Clinical Exercises、第一版"医学書院、東京. 181 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] 橋本隆: "内科医のための皮膚病変のみかた"文光堂、東京. 197 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 橋本隆: "皮膚科診療プラクティス「9.やさしい小児皮膚科学」"文光堂、東京. 282 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 安元慎一郎,橋本隆: "粘膜疾患診療マニュアル"Monthly Derma. 80 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hirako Y et al.: "Cleavage of BP180(Type XVII collagen) yields a 120kDa collagenous extracellular peptide"J Biol Chem. 273(16). 9711-9717 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Chan LS et al: "Epitope spreading; lessons from autoimmune skin diseases"J Invest Dermatol. 110. 103-109 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nousari HC et al.: "The mechanism of respiratory failure in paraneoplastic pemphigus"N Eng J Med. 340. 1406-1410 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nie Z,Hashimoto T: "Complementary peptide against the major epitope in NC16A of BP180 show no spidicificity as vaccines ot bulous pemphigoid"J Dermatol Sci. 21. 157-164 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hashimoto T: "Mini-sympsium issue of review articles in the Journal of Dermatological Science-Skin diseases related to abnormality in desmosomes and hemidesmosomes-ediforial review"Dermatol Sci. 20. 81-84 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nie Z,Hashimoto T et al.: "C-terminus of Desmoyokin/AHNAK protein is mainly located in the nucleus in low calcium condition,but low to normal calcium shift translocates a part of it to cytoplasm"J Invest Dermatol. (印刷中).

    • Related Report
      1999 Annual Research Report
  • [Publications] 橋本 隆: "KEY WORD皮膚疾患"先端医学. 210 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 橋本 隆: "皮膚科診療プラクティス"文光堂. 305 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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