| Project/Area Number |
16K07084
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Laboratory animal science
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| Research Institution | Microbial Chemistry Research Foundation (2017-2018)
The University of Tokyo (2016) |
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Principal Investigator |
NAKANISHI Tomoko 公益財団法人微生物化学研究会, 微生物化学研究所, 博士研究員 (10344863)
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| Co-Investigator(Kenkyū-buntansha) |
斎藤 泉 公益財団法人微生物化学研究会, 微生物化学研究所, チームリーダー (70158913)
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| Research Collaborator |
KAI Chieko
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 麻疹ウイルス / ゲノム編集 / CRISPR/Cas9システム / NSG / 免疫ヒト化マウス / CRISPR/Cas9 / MHC / 白血球減少 / 感染モデル / GFP / ヒト化マウス / 臍帯血幹細胞 |
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| Outline of Final Research Achievements |
Natural hosts of measles virus (MV) are only humans and no other animals except nonhuman primates have susceptibility to MV infection. To study the mechanisms of MV pathogenicity, we aimed to establish a small animal model for MV infection by utilizing mice with reconstituted human immune system components (humanized mice).
When we challenged the humanized mice with a recombinant wild-type MV expressing EGFP, a strong EGFP fluorescence was found in spleen, lymph nodes, and bone marrow. The fluorescence was confirmed to associate with MV infection of human T and B cells. Number of human lymphocytes were decreased and subsequently recovered. Moreover, Green fluorescent spots similar to skin rashes were observed in the abdominal skin. The spots were found to be due to accumulation of human lymphocytes to the hair follicles. These results indicate that our small animal model would be useful for elucidating the mechanism of MV infection and its pathogenicity.
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| Academic Significance and Societal Importance of the Research Achievements |
免疫ヒト化マウスを利用した麻疹ウイルス感染モデルは、これまでのモデルと比較して簡便に利用できる小動物モデルである。また、改良型免疫ヒト化マウスは、移植するヒト臍帯血幹細胞との間のHLAを一致させるものであり、獲得免疫存在下で、麻疹ウイルスのみならずヒト白血病ウイルスやデングウイルスなどのヒト血球系ウイルスの感染機構解明や予防・治療法の開発、がんの治療法開発などに広く応用できると期待される。
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