1999 Fiscal Year Final Research Report Summary
Establishment of Model Mice of Rheumatoid Arthritis by using nonstructural protein 1 (NS1) of parvovirus B19
| Project/Area Number |
10470074
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Virology
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| Research Institution | Tohoku University |
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Principal Investigator |
SUGAMURA Kazuo Tohoku University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (20117360)
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| Co-Investigator(Kenkyū-buntansha) |
ASAO Hironobu Tohoku University, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (80250744)
ISHII Naoto Tohoku University, Graduate School of Medicine, Research Associate, 大学院・医学系研究科, 助手 (60291267)
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| Project Period (FY) |
1998 – 1999
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| Keywords | parvovirus / rheumatoid arthritis / apoptosis / hydrops fetalis |
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| Research Abstract |
Human parvovirus B19 (B19) infection causes a wide variety of human diseases including erythema infectiosum, aplastic crises and nonimmune hydrops fetalis (NIHF). Epidemiological studies of B19 virus has suggested a possible relationship between B19 infection and rheumatoid arthritis (RA). Since B19 virus produces one major nonstructural protein, NS1, which is known to harbor functions of apoptotic cytotoxicity and transcriptional activator, we suspect that NS1 plays an important role in the occurrence of infectious diseases caused by B19 virus. In this research project, we attempted to generate NS1 transgenic mice, which develop NHIF and RA. We first generated transgenic mice of NS1, of which expression is controlled by the GATA1-promoter. A line of NS1-Tg mice showed embryonic lethality within E6.5, and two other lines were also embryonically lethal between E14.5 and E15.5 with severe anemias. These phenotypes of NS1-Tg mice resemble those of human NIHF, suggesting that the NS1-Tg mice are a useful model for human NIHF. We also generated another type of NS1-Tg mice, in which NS1 expression is regulated by the immunoglobulin promoter in B lymphocytes. They expressed NS1 mRNA in lymphoid cells, but expression of NS1 protein was undetectable. Up until 40 weeks of age, they did not develop any signs of RA or any other autoimmune diseases. Since their expression of NS1 may be too low to induce any pathology in these mice, we are trying to generate other lines of NS1-Tg mice, which express higher amounts of NS1.
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Research Products
(6 results)
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[Journal Article] Serologic Study of Human Parvovirus B19 Infection in Pregnancy in Japan,1999
Author(s)
Yaegashi, N., Niinuma, T., Chisaka, H., Uehara, S., Okamura, K., Shinkawa, O., Tsunoda, A., Moffatt, S., Sugamura, K.Yajima, A.
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Journal Title
J.Infection Vol.38
Pages: 30-35
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Parvovirus B19 induces poptosis of erythroid cells in vitro and in vivo.1999
Author(s)
Yaegashi, N., Niinuma, T., Chisaka, H., Uehara, S., Moffatt, S., Tada, K., Iwabuchi, M., Matsunaga Y., Nakayama, M., Yutani, C., Osamura, Y., Hirayama, E., Okamura, K., Sugamura, K., Yajima, A.
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Journal Title
J.Infection Vol.39
Pages: 68-76
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Human parvovirus B19 as a causative agent for rheumatoid arthritis.1998
Author(s)
Takahashi, Y., Murai, C., Shibata, S., Munakata, Y., Ishii, T., Ishii, K., Saitoh, T., Sawai, T., Sugamura, K., Sasaki, T.
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Journal Title
Proc.Natl.Acad.Sci.USA, Vol.95, 14
Pages: 8227-8232
Description
「研究成果報告書概要(欧文)」より
