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Development of transgenic animals of complement regulatory molecules.

Research Project

Project/Area Number 07557337
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section試験
Research Field Immunology
Research InstitutionNagoya City University

Principal Investigator

OKADA Noriko  Nagoya City Univ.School of Medicine, Assistant, 医学部, 助手 (20160682)

Co-Investigator(Kenkyū-buntansha) TAKAGI Hiroshi  Nagoya Univ.School of Medicine, Professor, 医学部, 教授 (70154755)
HASHIMOTO Takashi  Nagoya City Univ.School of Medicine, Assistant Professor, 医学部, 助教授 (10094393)
OKADA Hidechika  Nagoya City Univ.School of Medicine, Professor, 医学部, 教授 (30160683)
NONAKA Masaru  Nagoya City Univ.School of Medicine, Assistant Professor, 医学部, 助教授 (40115259)
Project Period (FY) 1995 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1996: ¥2,300,000 (Direct Cost: ¥2,300,000)
Keywordsxenotransplantation / complement / regulatory molecules / DAF / Crry / MCP / トランスジェニック動物 / 異種移植 / 種特異的補体制御膜因子 / 補体活性化
Research Abstract

Complement plays an essential role in the acute rejection of discordant xenotransplants. To overcome this problem, development of transgenic animals have been generated which have cDNA of the species specific membrane inhibitors of human. However, to detarmine its applicability to suppress the acute rejection of xenotransplants, experimental models of xenotransplantation between experimental animals.
For this purpose, gene cloning of the species specific membrane inhibitors is an essential requirement. We have already cloned the cDNA of rat 512 antigen (512Ag) which restricts C3 convertase of rat complement. In this research project we have indentified guinea pig DAF (GP-DAF) with monoclonal antibody (mAb), and its cDNA has been successfully cloned demonstrating that GP-DAF is comprised of several isotypes due to the alternative splicing. Furthermore, we have successfully cloned cDNA of guinea pig MCP (GP-MCP), mouse DAF,mouse CD59 and rat DAF.
Using these cDNA,we have prepared CHO cells transfected with cDNA of rat 512Ag, GP-DAF and GP-MCP,and these cells have been demonstrated to be registant to the serum complement homologous to the genes expressed on the transfectants.

Report

(3 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report
  • Research Products

    (51 results)

All Other

All Publications (51 results)

  • [Publications] Nishikawa,K.: "Local inflammation caused by a monoclonal antibody which blocks the function of the rat membrane inhibitor of C3 convertase." J.Immunol.156. 1182-1188 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Fukuoka,Y.: "Molecular cloning of murine decay accelerating factor(DAF)by immunoscreening." Int.Immunol.8. 379-385 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Nakamura,M.: "Quantification of the CD55 and CD59,membrane inhibitors of complement on HIV-1 particles as a function of complement-mediated virolysis." Microbiol Immunol.40. 561-567 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Iwata,M.: "Complement plays an essential role in shock following intestinal ischaemia in rats." Clin.Exp.Immunol.106. 156-159 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Hosokawa,M.: "Molecular cloning of guinea pig membrane cofactor protein(MCP):Preferential expression in testis." J.Immunol.157. 4946-4952 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Rogers,C.A.: "Expression and function of membrane regulators of complement on rat astrocytes in culture." Immunology. 88. 153-161 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Hayashi,S.: "Protection of guinea pig cells from rat complement-mediatedlysis by the transfection of rat complement regulatory factor 5I2 gene." Xenotransplanmtation. 3. 217-221 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Wu,X.: "IgM natural antibody against an asialo-oligosaccharide,gangliotetraose(Gg4)sensitize HIV-I infected cells for cytolysis by homologous complement." Int.Immunol.8. 153-158 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Okada,N.: "Presence of IgM antibodies which sensitize HIV-1 infected cells to cytolysis by homologous complement in long term survivors of HIV-infection." Microbiol.Immunol.41(in press). (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Akatsu,H.: "Unique expression of HRF20(CD59)in human nervous tissue." Microbiol.Immunol.41(in press). (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Nangaku,M.: "Overexpression of Crry protects mesangeal cells from complement mediated injury." J.Am.Soc.Neuphrol.(in press). (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Okada,N.: "A monoclonal antibody which blocks the complement regulatory activity of guinea pig erythrocytes and characterization as guinea pig decay accelerating factor." J.Immunol.154. 6103-6111 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Nomura,A.: "Tubulointerstitial injury induced in rays by a monoclonal antibody which inhibits function of a membrane inhibitor of complement." J.Clin.Inv.96. 2348-2356 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 野中真弓: "分子アレルギー学 補体の分子生物学(分担)" Medical Review社(印刷中), (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 岡田則子: "バイオデイフェンスシリーズ1 ヒトと動植物のデイフェンス・・巧妙な異物との戦い" 菜根出版(印刷中), (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Okada, N., Tanaka, H., Takizawa, H.and Okada, H.: "A monoclonal antibody which blocks the complement regulatory activity of guinea pig erythrocytes and characterization as guinea pig decay accelerating factor" J.Immunol.154. 6103-6111 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Nishikage, H., Baranyi, L., Okada, H., Okada, N., Isobe, , K., Nomura, A., Yoshida, F.and Matsuo, S.: "The role of a complement regulatory protein in rat mesengeal glomerulonephritis." J.Am.Soc.Nephrol.6. 234-242 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Nonaka, M., Miwa, T., Okada, N., Nonaka, M.and Okada, H.: "Multiple isoforms of guinea pig decay-accelerating factor (DAF) generated by alternative splicing." J.Immunol.155. 3037-3048 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kaneko, Y., Okada, N., Baranyi, L., Azuma, T.and Okada, H.: "Antagonistic peptides against human anaphylatoxin C5a." Immunology. 86. 149-154 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Nomura, A., Nishikawa, K., Yuzawa, Y., Okada, H., Okada, N., Morgan, B.P., piddlesden, S.J., Nadai, M., Hasegawa, T.and Matsuo, S.: "Tubulointerstitial injury induced in rats by a monolonal antibody which inhibits function of a membrane inhibitor of complement." J.Clin.Inv.96. 2348-2356 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Wu, X., Okada, N., Iwamori, M.and Okada, H.: "IgM natural antibody against an asialo-oligosaccharide, gangliotetraose (Gg4) sensitizes HIV-I infected cells for cytolysis by homologous complement." Int.Immunol.8. 153-158 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Nishikawa, K., Matsuo, S., Okada, N., Morgan, B.P.And Okada, H.: "Local inflammation caused by a monoclonal antibody which blocks the function of the rat membrane inhibitor of C3 convertase." J.Immunol.156. 1182-1188 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Fukuoka, Y., Yasui, A., Okada, N.and Okada, H.: "Molecular cloning of murine decay accelerating factor (DAF) by immunoscreening." Int.Immunol.8. 379-385 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Hayashi, S., Okada, H., Emi, N., Okada, N., Yokoyama, I.and Takagi, H.: "Protection of guinea pig cells from rat complement-mediated lysis by the transfection of rat complement regulatory factor 512 gene." Xenotransplanmtation. 3. 217-221 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Rogers, C.A., Gasque, P., Piddlesden, S.J., Okada, N., Holers, V.M.and Morgan, B.P.: "Expression and function of membrane regulators of complement on rat astrocytes in culture." Immunology. 88. 153-161 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Nakamura, M., Okada, H., Sasaki, H., Yoshida, K., Kamada, M., Okada, N., Terada, M.and Ohno, T.: "Quantification of the CD55 and CD59, membrane inhibitors complement on HIV-1 particles as a function of complement-mediated virolysis." Microbiol Immunol.40. 561-567 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Iwata, M., Itoh, M., Joh, Y., Yokoyama, Y., Okada, N.and Okada, H.: "Complement plays an essential role in shock following intestinal ischaemia in rats." Clin.Exp.Immunol.106. 156-159 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Hosokawa, M., Nonaka, M., Okada, N., Nonaka, M.and Okada, H.: "Molecular cloning of guinea pig membrane cofactor protein (MCP) : Preferential expression in testis." J.Immunol.157. 4946-4952 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Nangaku, M., Quigg, R.J., Shankland, S.J., Okada, N., Johnson, R.J.and Couser, W.G.: "Overexpression of Crry protects mesangeal cells from complement mediated injury." J.Am.Soc.Nephrol.8. 223-233 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Okada, N., Wu, X.and Okada, H.: "Presence of IgM antibodies which sensitize HIV-1 infected cells to cytolysis by homologous complement in long term survivors of HIV-infection." Microbiol.Immunol.41 (in press). (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Akatsu, H., Yamada, T., Okada, N., Yamamoto, T., Yamashina, M.and Okada, H.: "Unique expression of HRF20 (CD59) in human nervous tissue." Microbiol.Immunol.41 (in press). (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Nishikawa, K.: "Local inflammation caused by a monoclonal antibody which blocks the function of the rat membrane inhibitor of C3 convertase." J. Immunol.156. 1182-1188 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Fukuoka, Y.: "Molecular cloning of murine decay accelerating factor (DAF) by immunoscreening." Int. Immunol.8. 379-385 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Nakamura, M.: "Quantification of the CD55 and CD59, membrane inhibitors of complement on HIV-1 particles as a function of complement-mediated virolysis." Microbiol Immunol.40. 561-567 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Iwata, M.: "Complement plays an essential role in shock following intestinal ischaemia in rats." Clin. Exp. Immunol.106. 156-159 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Hosokawa, M.: "Molecular cloning of guinea pig membrane cofactor protein (MCP) : Preferential expression in testis." J. Immunol.157. 4946-4952 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Rogers, C. A.: "Expression and function of membrane regulators of complement on rat astrocytes in culture." Immunology. 88. 153-161 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Hayashi, S.: "Protection of guinea pig cells from rat complement-mediated lysis by the transfection of rat complement regulatory factor 512 gene." Xenotransplanmtation,. 3. 217-221 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Wu,X.: "IgM natural antibody against an asialo-oligosaccharide, gangliotetraose (Gg4) sensitizes HIV-I infected cells for cytolysis by homologous complement." Int. Immunol.8. 153-158 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Okada, N.: "Presence of IgM antibodies which sensitize HIV-1 infected cells to cytolysis by homologous complement in long term survivors of HIV-infection." Microbiol. Immunol.41(in press). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Akatsu, H.: "Unique expression of HRF20 (CD59) in human nervous tissue." Microbiol. Immunol.41(in press). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Nangaku, M.: "Overexpression of Crry protects mesangeal cells from complement mediated injury." J. Am. Soc. Nephrol.(in press). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] 野中真弓: "分子アレルギー学 補体の分子生物学(分担)" Medical Review社(印刷中), (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Okada,N.: "A monoclonal antibody which blocks the complement regulatory activity of guinea pig erythrocytes and characterization as guinea pig decay accelerating factor." J.Immunol.154. 6103-6111 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Dohi,N.: "Novel variation in rat complement regulatory membrane protein,5I2 antigen(rat Crry)mRNA." FASEBJ.9. 807 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Nomura,A.: "Tubulointerstitial injury induced in rats by a monoclonal antibody which inhibits function of a membrane inhibitor of complement." J.Clin.Inv.96. 2348-2356 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Nishikage,H.: "The role of a complement regulatory protein in rat mesangial glomerulonephritis." J.Am.Soc.Nephrol.6. 234-242 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Nonaka,M.: "Multiple isoforms of guinea pig decay-accelerating factor(DAF)fenerated by alternative splicing." J.Immunol.155. 3037-3048 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Nishikawa,K.: "Local inflammation caused by a monoclonal antibody which blocks the function of the rat membrane inhibitor of C3 convertase." J.Immunol.156. 1182-1188 (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] 服部義郎: "最新内科学大系74 関節疾患" 中山書店, 368 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 岡田則子: "バイオデイフェンスシリーズ1 ヒトと動植物のデイフェンス・・巧妙な異物との戦い" 菜根出版(印刷中), (1996)

    • Related Report
      1995 Annual Research Report

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

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