2004 Fiscal Year Final Research Report Summary
EXPRESSION OF HUMAN ENDOGENOUS RETROVIRUS AND ITS POSSIBLE ROLES FOR DEVELOPING AUTOIMMUNE DESIASES
| Project/Area Number |
15590330
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | HOKKAIDO UNIVERSITY |
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Principal Investigator |
TOMARU Utano Hokkaido Univ., Grad.School of Med., Lecturer, 大学院・医学研究科, 講師 (20360901)
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| Co-Investigator(Kenkyū-buntansha) |
ISHIZU Akihiro Hokkaido Univ., Grad.School of Med., Lecturer, 大学院・医学研究科, 講師 (60321957)
SUZUKI Akira Hokkaido Univ., Grad.School of Med., Instructor, 大学院・医学研究科, 助手 (50374236)
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| Project Period (FY) |
2003 – 2004
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| Keywords | human endogenous retrovirus / transgenic rat / tissue-specific expression / targeted antigen / autoimmune disease |
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| Research Abstract |
The aims of this project were to investigate the biological role of human endogenous retrovinis-R (HERV-R) in vivo. We have established transgenic rats carrying a full sequence of HERV-R under control of its own long terminal repeat promoter (HERV-R rat), and analyzed HERV-R expression and its possible roles for developing autoirnmune disease. Major research accomplishments were as follows :
1.The product of the transgene was detected as an 85 kDa glycoprotein in specific organs such as Harderian gland, prostatic gland, skin and salivary gland.
2.We have found that skin tissues transplanted from HERV-R rats to wild rats are rejected around 50 days after transplantation, suggesting that HERV-R antigen is recognized as a target antigen in the immune responses.
3.Because we observed no pathological significance in the HERV-R rats, we have established double transgenic rats carrying both human infectious retrovirus HTLV-I env-pX gene and HERV-R gene. Based on our previous studies, transgenic rat carrying HTLV-I env-pX gene indicate significant pathological findings which are similar to human autoimmune disorders. We have postulated that HERV-R antigen may modulate immune responses in the rats with a background of auto-immune responses. We observed that double transgenic rats had a tendency to be short-lived, and we found deposition of IgM-type autoantibodies in the Harderian gland. We also found thrombus formation in the glomeruli of kidney by histopathological analysis.
4.Based on our experiments, we propose a possibility that expression of endogenous retrovirus may modulate immune responses in the inflammatory diseases including autoimmune disorders.
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Research Products
(26 results)
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[Journal Article] Hematopoietic progenitor cells as possible origins of epithelial thymoma in a human T lymphocyte virus type I pX gene transgenic rat model.2004
Author(s)
Tsuchikawa, T., Ikeda, H., Kikuchi, K., Tsuji, T., Baba, T., Ishizu, A., Tanaka, Y., Kate, H, Yoshiki, T.
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Journal Title
Lab Invest 84
Pages: 245-252
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Bone marrow cells carrying the env-pX transgene play a role in the severity but not prolongation of arthritis in human T-cell leukaemia virus type-I transgenic rats : a possible role of articular tissues carrying the transgene in the prolongation of arthritis.2004
Author(s)
Abe, A., Ishizu, A., Ikeda, H., Hayase, H., Tsuji, T., Miyatake, Y., Tsuji, M., Fugo, K., Sugaya, T., Higuchi, M., Matsuno, T., Yoshiki, T.
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Journal Title
Int J Exp Pathol 85(4)
Pages: 191-200
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Differential modulation of gene expression among rat tissues with warm ischemia.2004
Author(s)
Miyatake, Y., Ikeda, H., Michimata, R., Koizumi, S., Ishizu, A., Nishimura, N., Yoshiki, T.
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Journal Title
Exp Mol Pathol 77(3)
Pages: 222-230
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Increased expression of human T lymphocyte virus type I (HTLV-I) Tax11-19 peptide-human histocompatibility leukocyte antigen A^*201 complexes on CD4+ CD25+ T Cells detected by peptide-specific, major histocompatibility complex-restricted antibodies in patients with HTLV-I-associated neurologic disease.2004
Author(s)
Yamano, Y., Cohen, C.J., Takenouchi, N., Yao, K., Tomaru, U., Li, H.C., Reiter, Y., Jacobson, S.
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Journal Title
J Exp Med 199(10)
Pages: 1367-1377
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Transduction of dominant negative ATF-1 suppresses the pX gene expression in joint fibroblastic cells derived from HTLV-I transgenic rats.2003
Author(s)
Ishizu, A., Tsuji, T., Abe, A., Saito, S., Takahashi, T., Ikeda, H., Meruelo, D., Yoshiki, T.
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Journal Title
Exp Mol Pathol 74
Pages: 309-313
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Functional alteration of peripheral CD25^+CD4^+ immunoregulatory T cells in a transgenic rat model of autoimmune diseases.2003
Author(s)
Higuchi, M., Ishizu, A., Ikeda, H., Hayase, H., Fugo, K., Tsuji, M., Abe, A., Sugaya, T., Suzuki, A., Takahashi, T., Koike, T., Yoshiki, T.
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Journal Title
J Autoimmunity 20
Pages: 43-49
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Tissue specific high level expression of a full length human endogenous retrovirus genome transgene, HERV-R, under control of its own promoter in rats.2003
Author(s)
Tanaka, S., Ikeda, H., Otsuka, N., Yamamoto, Y., Sugaya, T., Yoshiki, T.
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Journal Title
Transgenic Research 12
Pages: 319-328
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Vaccination of fusion cells of rat dendritic and carcinoma cells prevents tumor growth in vivo.2003
Author(s)
Kawada, M., Ikeda, H., Takahashi, T., Ishizu, A., Ishikura, H., Katoh, H., Yoshiki, T.
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Journal Title
Int J Cancer 105
Pages: 520-526
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] In vitro model of suicide gene therapy for alpha-fetoproteinproducing gastric cancer.2003
Author(s)
Nakaya, H., Ishizu, A., Ikeda, H., Tahara, M., Shindo, J., Itoh, R., Takahashi, T., Asaka, M., Hiroshi, I., Yoshiki, T.
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Journal Title
Anticancer Res. 23
Pages: 3795-3800
Description
「研究成果報告書概要(欧文)」より
