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Development and analyses of novel animal models for human retrovirus-induced desiases.

Research Project

Project/Area Number 14207010
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Experimental pathology
Research InstitutionHOKKAIDO UNIVERSITY

Principal Investigator

KYOSHIKI Takashi  Hokkaido Univ., Grad.School of Med., Prof., 大学院・医学研究科, 教授 (60220612)

Co-Investigator(Kenkyū-buntansha) TOMARU Utano  Hokkaido Univ., Grad.School of Med., Inst., 大学院・医学研究科, 助手 (20360901)
ISHIZU Akihiro  Hokkaido Univ., Grad.School of Med., Lec., 大学院・医学研究科, 講師 (60321957)
IKEDA Hitoshi  Hokkaido Univ., Grad.School of Med., Asso.Prof., 大学院・医学研究科, 助教授 (20232192)
高橋 利幸  北海道大学, 大学院・医学研究科, 講師 (40261284)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥43,290,000 (Direct Cost: ¥33,300,000、Indirect Cost: ¥9,990,000)
Fiscal Year 2003: ¥20,150,000 (Direct Cost: ¥15,500,000、Indirect Cost: ¥4,650,000)
Fiscal Year 2002: ¥23,140,000 (Direct Cost: ¥17,800,000、Indirect Cost: ¥5,340,000)
Keywordsretrovirus / HTLV-I / HIV-1 / animal model / myelopathy / transgenic / autoimmune disease / thymoma / HIV-I / 免疫制御細胞 / レトロウィルス / Cyclin T1
Research Abstract

Virus-host interactions were investigated using rat models for human retrovirus-induced diseases.
1.HAM rat disease occurred in HTLV-I-infected rats in a strain-dependent manner. In HAM susceptible rats, expression of the INF-γ gene in the spinal cord did not increase after HTLV-I infection, while did in HAM resistant strains. These findings suggest that INF-γ may play a role in prevention at HTLV-1-induced diseases.
2.Autoimmune diseases occurred in HTLV-I LTR-env-pX transgenic rats (LTR-env-pX rats). Functional alteration of CD25+CD4+ immunoregulatory T-cells was evident in LTR-env-pX rats before they developed diseases. Expressions of the CTLA-4, GITR, Foxp3, and SOCS family genes in the cells of LTR-env-pX rats were lower than those of wild type rats. Synovial tissues rather than bone marrow cells carrying the transgene may play roles in prolongation of arthritis developed in LTR-env-pX rats.
3.Benign epithelial thymoma occurred in lck-pX transgenic rats (lck-pX rats). Thymoma grafted in the subcapsular space of the kidney of lck-pX rats showed malignant transformation. The p16/ARF genes were lost in the transformed tumors, thus suggesting that these molecules may be associated with malignant transformation of HTLV-I-induced neoplasms.
4.Rat fibrobalastic cells expressing human CD4 and CXCR-4/CCR5 could be infected with HIV-1. Although HIV-1 provirus was integrated in the genome of these cells, viral expression was not achieved completely. Putative factors including human cyclin T1 and MHC class II transactivator (C2TA) may be needed for viral replication in the cells. To examine interactions of HIV-1 and host in vivo, transgenic rats carrying the human CD4, CXCR4/CCR5, cyclic T1, and C2TA genes were established.

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (53 results)

All Other

All Publications (53 results)

  • [Publications] Fugo K et al.: "The role of the thymus in development of necrotizing arteritis in transgenic rats carrying the env-pX gene of human T cell leukemia virus type I."Am J Pathol. 161. 755-761 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sugaya T et al.: "Clonotypic analysis of T cells accumulating at arthriticlesions in HTLV-I env-pX transgenic rats."Exp Mol Pathol. 72. 56-61 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ogawa Y et al.: "Elution of IgA from the kidney tissue exhibiting a glomerular IgA deposition and analysis of the antibody specificity."Pathobiology. 70. 98-102 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kikuchi K et al.: "A novel animal model of thymic tumor : development of epithelial thymoma in transgenic rats carrying human T lymphocyte virustype I."Int J Exp Pathol. 83. 247-255 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yoshiki T.: "Etiopathogenesis of necrotizing vasculitis."Intern Med. 41. 39-40 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Higuchi M et al.: "Functional alteration of peripheral CD25+CD4+ immunoregulatory T cells in a transgenic rat model of autoimmune diseases."J Autoimmun. 20. 43-49 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ishizu A et al.: "Transduction of dominant negative ATF-1 suppresses the pX gene expression in joint fibroblastic cells derived from HTLV-I transgenic rats."Exp Mol Pathol. 74. 309-313 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tanaka S et al.: "Tissue specific high level expression of a full length human endogenous retrovirus genome transgene, HERV-R, under control of its own promoter in rats."Transgenic Res. 12. 319-328 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yang L et al.: "Epstein-Barr virus infection of rat lymphocytes expressing human CD21 results in restricted latent virus gene expression but not in immunoblastic transformation."J Med Virol. 70. 126-130 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kawada M et al.: "Vaccination of fusion cells of rat dendritic and carcinoma cells prevents tumor growth in vivo."Int J Cancer. 103. 520-526 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nakaya H et al.: "In vitro model of suicide gene therapy for alpha-fetoprotein-producing gastric cancer."Anticancer Res. 23. 3795-3800 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tomaru U et al.: "Provirus expansion and deregulation of apoptosis-regulated genes in the spinal cord of a rat model for human T lymphocyte virus type I-associated myeloneuropathy."J Neurovirol. 9. 530-538 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tsuchikawa T et al.: "Hematopoietic progenitor cells as possible origins of epithelial thymoma in a human T lymphocyte virus type I pX gene transgenic rat model."Lab Invest. 84. 245-252 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yoshiki T.: "Monograph on Cancer Research No. 50. Two decades of adult T-cell leukemia and HTLV-1 research (Edited by Kazuo Sugamura, Takashi Uchiyama, Masao Matsuoka, and Mari Kannagi.)"Japan Scientific Societies Press, Karger. 366 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yamano Y et al.: "Monograph on Cancer Research No. 50. Two decades of adult T-cell leukemia and HTLV-1 research (Edited by Kazuo Sugamura, Takashi Uchiyama, Masao Matsuoka, and Mari Kannagi.)"Japan Scientific Societies Press, Karger. 366 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yoshiki T.: "Hokkaido University Medical Library Series vol. 47. Molecular Pathology of Human Retroviruses, HTLV-I and Endogenous Retroviruses."Hokkaido University Graduate School of Medicine. 106 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yoshiki T.: "Hokkaido University Medical Library Series vol. 48. Progress in Cancer Pathobiology and Transplantation Immunobiology."Hokkaido University Graduate School of Medicine. 142 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Fugo K et al.: "The role of the thymus in development of necrotizing arthritis in transgenic rats carrying the env-pX gene of human T cell leukemia virus type I"Am.J.Pathol.. 161(3). 755-761 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sugaya T et al.: "Clonotypic analysis of T cells accumulating at arthritic lesions in HTLV-I env-pX transgenic rats."Exp.Mol.Pathol.. 72(1). 56-61 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ogawa Y et al.: "Elution of IgA from kidney tissues exhibiting glomerular IgA deposition and analysis of antibody specificity."Pathobiology. 70(2). 98-102 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kikuchi K et al.: "A novel animal model of thymic tumor development of epithelial thymoma in transgenic rats carrying human T lymphocyte virus type I pX gene."Int.J.Exp.Pathol.. 83(5). 247-255 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yoshiki, T.: "Etiopathogenesis of necrotizing vasculitis."Int.Med.. 41(1). 39-40 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Higuchi M et al.: "Functional alteration of peripheral CD25+CD4+immunoregulatory T cells in a transgenic rat model of autoimmune diseases."J.Autoimmun.. 20(1). 43-49 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ishizu A et al.: "Transduction of dominant negative ATF-1 suppresses the pX gene expression in joint fibroblastic cells derived from HTLV-I transgenic rats."Exp.Mol.Pathol.. 74(3). 309-313 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tanaka S et al.: "Tissue specific high level expression of a full human endogenous retrovirus genome transgene, HERV-R, under control of its own promoter in rats."Transgenic Res.. 12(3). 319-328 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yang L et al.: "Epstein-Barr virus infection of rat lymphocytes expressing human CD21 results in restricted latent virus gene expression but not in immunoblastic transformation."J.Med.Virol.. 70(1). 126-130 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kawada M et al.: "Vaccination of fusion cells of rat dendritic and carcinoma cells prevents tumor growth in vivo."Int.J.Cancer.. 105(4). 520-526 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nakaya H et al.: "In vitro model of suicide gene therapy for alpha-fetoprotein producing gastric cancer."Anticancer Res.. 23(5A). 3795-3800 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tomaru U et al.: "Provirus expansion and deregulation of apoptosis regulated genes in the spinal cord of a rat model for human T lymphocyte virus type I-associated myeloneuropathy."J.Neurovirol.. 9(5). 530-538 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tsuchikawa T et al.: "Hematopoietic progenitor cells as possible origins of epithelial thymoma in a human T lymphocyte virus type I pX gene transgenic rat model."Lab.Invest.. 84(2). 245-252 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yoshiki T.: "Two decades of adult T-cell leukemia and HTLV-I research."Monograph on Cancer Research. No.50. 366 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yamano Y et al.: "Two decades of adult T cell leukemia and HTLV-I research."Monograph on Cancer Research. No.50. 366 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yoshiki T.: "Molecular Pathology of Human Retroviruses, HTLV-I and Endogenous Retroviruses."Hokkaido University Medical Library Series. vol.47. 106 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yashiki T.: "Progress in Cancer Pathology and Transplantation Immunobiology."Hokkaido University Medical Library Series. vol.48. 142 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nakaya, H., et al.: "In vitro model of suicide gene therapy for alpha-fetoprotein-producing gastric cancer"Anticancer Research. 23. 3795-3800 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 石津明洋, 吉木 敬: "ウイルス誘発のモデル動物"医学のあゆみ. 206・2. 143-145 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yoshiki, T.: "Pathogenesis of HAM/TSP in a rat model"Gann Monograph on Cancer Research. 50. 183-196 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tsuchikawa, T., et al.: "Hematopoietic progenitor cells as possible origins of epithelial thymoma in a human T lymphocyte virus type I pX gene transgenic rat model"Laboratory Investigation. 84・2. 245-252 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ishizu, A., et al.: "Transduction of dominant negative ATF-1 suppresses the pX gene expression in joint fibroblastic cells derived from HTLV-I transgenic rats"Experimental Molecular Pathology. 74. 309-313 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Higuchi, M., et al.: "Functional alteration of peripheral CD25+CD4+immunoregulatory T cells in a transgenic rat model of autoimmune diseases"Journal of Autoimmunity. 20. 43-49 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tanaka, T., et al.: "Tissue specific high level expression of a full human endogenous retrovirus genome transgene, HERV-R, under control of its own promoter in rats"Transgenic Research. 12. 319-328 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yang, L., et al.: "Epstein Barr virus infection of rat lymphocytes expressing human CD21 results in restricted latent virus gene expression but not in immunoblastic transformation"Journal of Medical Virology. 70. 126-130 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kawada, M., et al.: "Vaccination of fusion cells of rat dendritic and carcinoma cells prevents tumor growth in vivo"International Journal of Cancer. 105. 520-526 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tomaru, U., et al.: "Provirus expansion and deregulation of apoptosis-regulated genes in the spinal cord of a rat model for human T lymphocyte virus type I-associated myeloneuropathy"Journal of Neurovirology. 9. 530-538 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Fugo K et al.: "The role of the thymus in development of necrotizing arteritis in transgenic rats carrying the env-pX gene of human T cell leukemia virus type I"Am J Pathol. 161. 755-761 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Sugaya T et al.: "Clonotypic analysis of T cells accumulating at arthriticlesions in HTLV-I env-pX transgenic rats"Exp Mol Pathol. 72. 56-61 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ogawa Y et al.: "Elution of IgA from the kidney tissue exhibiting a glomerular IgA deposition and analysis of the antibody specificity"Pathobiolagy. 70. 98-102 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Higuchi1 M et al.: "Functional alteration of peripheral CD25+CD4+immunoregulatory T cells in a transgenic rat model of autoimmune diseases"J Autoimmun. 20. 43-49 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yang L et al.: "Epstein-Barr virus infection of rat lymphocytes expressing human CD21 results in restricted latent viral expression but not in immunoblastic transformation"J Med Virol. 70. 126-130 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ishizu A et al.: "Transduction of dominant negative ATF-1 suppresses the pX gene expression in joint fibroblastic cells derived from HTLV-I transgenic rats"Exp Mol Pathol. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kikuchi K et al.: "A novel animal model of thymic tumor : Development of epithelial thymoma in transgenic rats carrying human T lymphocyte virus type I pX gene"Int J Exp Pathol. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kawada M et al.: "Vaccination of fusion cells of rat dendritic and carcinoma cells prevents tumor growth in vivo"Int J Cancer. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tanaka S et al.: "Tissue specific high level expression of a full length human endogenous retrovirus genome transgene, HERV-R, under control of its own promoter in rats"Transgenic Res. (in press). (2003)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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