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Evaluation of the carbohydrate antigen-mediated donor rejection in xenotransplantation

Research Project

Project/Area Number 11557182
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Biological pharmacy
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

KOZUTSUMI Yasunori  Gradeate school of biostudies, Kyoto University, Professor, 生命科学研究科, 教授 (70205425)

Co-Investigator(Kenkyū-buntansha) TAKEMATSU Hiromu  Graduate school of Biostudies, Kyoto University, lnstructor, 生命科学研究科, 助手 (80324680)
SUZUKI Akemi  RIKEN Frontier, Group Director, フロンテイア研究システム, グループディレクター (70134533)
KAWASAKI Toshisuke  Pharmaceutical Sciences, Kyoto University, Professor, 薬学研究科, 教授 (50025706)
Project Period (FY) 1999 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥12,100,000 (Direct Cost: ¥12,100,000)
Fiscal Year 2001: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2000: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 1999: ¥5,400,000 (Direct Cost: ¥5,400,000)
Keywordssialic acid / xenotransplantation / NeuGc / Siglec / CD22 / 臓器移植 / CMP-NeuAC水酸化酵素 / B細胞 / N-グリコリルノイラミン酸 / N-アセチルノイラミン酸 / シアル酸水酸化酵素 / ノックアウトマウス / ヒト化マウス
Research Abstract

During the grant period, we conducted a research to evaluate the carbohydrate antigen-medi-ated donor organ rejection in the proposed xenoplantation procedure. Recently, shortage of donor organs from human source for the transplantation made xenoplantation (non-human to human transplantation) a rationale source of donor organ to be transplanted to meet the demand. Here, porcine is expected as the logical choice of animal for the preparation of donor organs because of their similarity in size and relative higher amino- acid sequence homology between human. However these two animal species considerably differ for their expression of the carbohydrate antigens in their cell surface. To verify the antigenicty of the N-glycolylneuraminic acid (NeuGc) which human lacks, we developed the mouse line lacking functional CMP-N-acetylneuraminic acid hydroxylase gene. Major achie- vements in this study are as follows.
(1) The targeted mutagenesis of CMP-NeuAc hydroxylase re-created the lack of NeuGc in human that is known to lack active hydroxylase and its product NeuGc in cells.
(2) We analyzed the immune system development in these mice that may affect the point of organ rejection and found that this mouse line has normal immune system in steady state.
(3) We backcrossed this ES-based germline mutation to C57Black/6 line to prepare the donor organ for organ transplantation. Now the number of generations backcrossed is 17 and back- ground similarity between donor and recipient is expected to be quite strong concerning types of MHC and other protein-based antigens.

Report

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

    (20 results)

All Other

All Publications (20 results)

  • [Publications] A.Kakio et al.: "Cholesterol-dependent formation of GM1 ganglioside-bound amyloid beta-protein, an endogenous seed for Alzheimer amyloid"J. Biol. Chem.. 276(27). 24985-24990 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] T.Yamaji et al.: "Apoptosis of CTLL-2 cells induced by an immunosuppressant, ISP-I, is caspase-3-like protease-independent"J. Biochem.. 129(4). 521-527 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] A.Ikeda et al.: "Identification and characterization of functional domains in a mixed lineage kinase LZK"FEBS Lett.. 488(3). 90-95 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] A.Ikeda et al.: "Mixed Lineage Kinase LZK Forms a Functional Signaling Complex with JIP-1, a Scaffold Protein of the c-Jun NH(2)-Terminal Kinase Pathway"J. Biochem.. 130・6. 773-781 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Y.Sun et al.: "Sli2(Ypk1), a homologue of mammalian protein kinase SGK, is a downstream kinase in the sphingolipid-mediated signaling pathway of years"Mol. Cell Biol.. 20・12. 4411-4419 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] T.Kanazawa et al.: "Inhibition of cytokinesis by a lipid metabolite, psychosine"J. Cell Biol.. 149・4. 943-950 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] A. Kakio et al.: "Cholesterol-dependent formation of GM1 ganglioside-bound amyloid beta- protein, an endogenous seed tor Alzheimer amyloid"J. Biol. Chem. 276(27). 24985-24990 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] T.Yamaji et al.: "Apoptosis of CTLL-2 cells induced by an immunosuppressant, ISP-I, is caspase-3-like protease-independent"J. Biochem.. 129(4). 521-527 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] A. Ikeda et al.: "Identification and characterization of functional domains in a mixed lineage kinase LZK"FEBS Lett. 488(3). 90-95 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] A. Ikeda et al.: "Mixed Lineage Kinase LZK Forms a Functional Signaling Complex with JIP-1, a Scaffold Protein of the c-Jun NH(2)-Terrminal Kinase Pathway"J. Biochem.. 130(6). 773-781 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Y. Sun et al.: "Sli2(Ypk1), a homologue of mammalian protein kinase SGK, is a downstream kinase in the sphingolipid-mediated signaling pathway of yeast"Mol. Cell Biol. 20(12). 4411-4419 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] T. Kanazawa et al.: "Inhibition of cytokinesis by a lipid metabolite, psychosine"J. Cell Biol.. 149(4). 943-950 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] A.Kakio et al.: "Cholesterol-dependent formation of GM1 ganglioside-bound amyloid beta-protein, an endogenous seed for Alzheimer amyloid"J. Biol. Chem.. 276・27. 24985-24990 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] T.Yamaji et al.: "Apoptosis of CTLL-2 cells induced by an immunosuppressant, ISP-I, is caspase-3-like protease-independent"J. Biol. Chem.. 129・4. 521-527 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] A.Ikeda et al.: "Identification and characterization of functional domains in a mixed lineage kinase LZK"FEBS Lett.. 488・3. 90-95 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] A.Ikeda et al.: "Mixed Lineage Kinase LZK Forms a Functional Signaling Complex with JIP-1, a Scaffold Protein of the c-Jun NH(2)-Terminal Kinase Pathway"J. Biochem.. 130・6. 773-781 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Y.Sun et al.: "Sli2/Ypk1, a homologue of mammalian protein kinase SGK, is a downstream kinase in the sphingolipid-mediated signal pathway of yeast"Mol.Cell.Biol.. 20(12). 4411-4419 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] T.Kanazawa et al.: "Inhibition of Cytokinesis by a Lipid Metabolite, Psychosine"J.Cell Biol.. 149(4). 943-950. (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Y.Ma et al.: "Antitumor activity of mannan-binding protein in vivo as revealed by a virus expression system: Mannan-binding proteindependent cell-mediated cytotoxicity"Proc. Natl. Acad. Sci. U.S.A. 96(2). 371-375 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Y.Sun et al.: "Sli2/Ypk1, a homologue of mammalian protein kinase SGK, is a downstream kinase in the sphingolipid-mediated signal pathway of yeast"Mol. Cell. Biol.. (in press). (2000)

    • Related Report
      1999 Annual Research Report

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

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