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1995 Fiscal Year Final Research Report Summary

ANALYSIS OF HTLV-I PATHOGENICITY USING ANIMAL MODELS

Research Project

Project/Area Number 06454188
Research Category

Grant-in-Aid for General Scientific Research (B)

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

Principal Investigator

YOSHIKI Takashi  Hokkaido University School of Medicine Professor, 医学部, 教授 (60220612)

Co-Investigator(Kenkyū-buntansha) IKEDA Hitoshi  Hokkaido University School of Medicine Instructor, 医学部, 助手 (20232192)
WAKISAKA Akemi  Hokkaido University School of Medicine Associate Professor, 医学部, 助教授 (90113646)
Project Period (FY) 1994 – 1995
KeywordsHTLV-I / Disease Model / HAM / TSP / Demyelination / Apoptosis / Transgenic Rat / Mammary Carcinoma / Autoimmune Diseases
Research Abstract

To investigate the pathogenesis of HTLV-I associated diseases, three rat models, HAM rat for HAM/TSP,mammary carcinoma developed pX rat for HTLV-I tumorigenicity, and autoimmune diseases developed env-pX rat for HTLV-I associated immunological disorders, were established by HTLV-I infection or transgenic technique.
1) HAM rat : In the spinal cords of WKAH rats carrying HTL-I infection, the apoptotic death of oligodendrocytes starting at 9 months after the infection was the first histopathological event before the demyelination. pX was selectively expressed in the diseased leasions, but not in others, even though provirus DNAs were consistently identified. TNF-alpha were frequently expressed in the diseased lesions. Moreover, both pX and TNF-alpha were expressed in the target leasions from 7 months after the infection. The collective evidence suggests that the apoptotic death of myelin forming cells in the target leasions by the selective activation of pX,and/or the production of TNF-alp … More ha is a major pathogenetic pathway of HAM rat disease.
2) pX rat : In transgenic rats carrying the pX gene under control of the mouse H-2 promoter, undifferentiated mammary carcinomas with granulocytic infiltration developed starting at 5 months of age. mRNAs of both pX and host genes, Gro and MIP-2, were highly expressed in the tumor tissue. Since expression and point mutation of several oncogenes and anti-oncogene were not demonstrated, hitherto unidentified novel oncogenic pathways may be activated in these pX rats.
3) env-pX rat : Transgenic rats carrying the env-pX gene, under control of own LTR,were established. Starting at 5 weeks of age, arthritis resembling RA,necrotizing arteritis resembling PN,polymyositis, myocarditis and Sjogren's syndrome-like sialo-and dacryoadenitis developed in env-pX rats. Thymic atrophy with severe depletion of CD4CD8 positive thymocytes was also observed. Autosntibodies, including rheumatoid factors and anti-dsDNA and anti-cardiolipin antibodies, were detected in the serum. The evidence indicztes that HTLV-I env-pX gene may cause these immunological disorders with autoimmune phenomenon. Less

  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Tateno,Y., Tateno,M: "Genetic and functional variabilities in the human immunodeficiency virus type 1 isolated from the same blood samples with and without CD8+cells." Immunol.Infect.Dis.4. 41-46 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kitamura,M.: "Expression of an endogenous retroviral gene product in human placenta." Int.J.Cancer.58. 836-840 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Seto,K., Abe,M.: "A rat model of HTLV-I infection. Development of chronic progressive myeloneuropathy in seropositive WKAH rats and related apoptosis." Acta Neuropahol.89. 483-490 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takeuchi,K.: "Expression of endogenous retroviruses, ERV3 and λ4-1, in synovial tissues from patients with rheumatoid arthritis." Clin.Exp.Immunol.99. 338-344 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yamada,S., Ikeda,H.: "Cytokine-producing mammary carcinomas in transgenic rats carrying the pX gene of human T-lymphotropic virus type I." Cancer Res.55. 2524-2527 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yoshiki,T.: "Chronic Progressive Myeloneuropathy in WKAH Rats Induced by HTLV-I Infection as an Animal Model for HAM/TSP in Humans." Intervirol.38. 229-237 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tateno, Y., Tateno, M., Ikuta, K., Yoshiki, T., Togashi, T., Matsumoto, S.: "Genetic and functional variabilities in the human immunodeficiency virus type 1 isolated from the same blood samples with and without CD8+cells." Immunol. Infect. Dis.4. 41-46 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kitamura, M., Maruyama, N., Shirasawa, T., Nagasawa, R., Watanabe, K., Tateno, M., Yoshiki, T.: "Expression of an endogenous retroviral gene product in human placenta." Int. J.Cancer.58. 836-840 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Seto, K., Abe, M., Ohya, O., Itakura, O., Ishigro, N., Ikeda, H., Wakisaka, A., Yoshiki, T.: "A rat model of HTLV-I infection. Development of chronic progressive myeloneuropathy in seropositive WKAH rats and related apoptosis." Acta Neurophol.89. 483-490 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takeushi, K., Katsumata, K., Ikeda, H., Minami, M., Wakisaka, A., Yoshiki, T.: "Expression of endogenous retroviruses, ERV3 and lambda4-1, in synovial tissues from patients with rheumatoid arthritis." Clin. Exp. Immunol.99. 338-344 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yamada, S., Ikeda, H., Yamazaki, H., Shikishima, H., Kikuchi, K., Wakisaka, A., Kasai, N., Shimotohno, K., Yoshiki, T.: "Cytokine-producing mammary carcinomas in transgenic rats carrying the pX gene of human T-lymphotropic virus type I." Cancer Res.55. 2524-2527 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoshiki, T.: "Chronic Progressive Myeloneuropathy in WKAH Rats Induced by HTLV-I Infection as an Animal Model for HAM/TSP in Humans." Intervirol.38. 229-237 (1995)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1997-03-04  

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