Reproduction of virus-specific immunodeficiency in humanized mice
| Project/Area Number |
25670198
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Experimental pathology
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| Research Institution | National Research Institute for Child Health and Development |
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Principal Investigator |
FUJIWARA Shigeyoshi 独立行政法人国立成育医療研究センター, その他部局等, その他 (30173488)
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| Co-Investigator(Renkei-kenkyūsha) |
IMADOME Ken-ichi 国立成育医療研究センター, 母児感染研究部, 室長 (70392488)
MATSUDA Go 国立成育医療研究センター, 母児感染研究部, 研究員 (60392130)
KANEGANE Hirokazu 東京医科歯科大学, 大学院医歯学総合研究科, 准教授 (00293324)
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | EBウイルス / ヒト化マウス / XIAP欠損症 / 免疫不全症 / サイトカイン / 血球貪食性リンパ組織球症 |
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| Outline of Final Research Achievements |
To reproduce EBV-related immunodeficiency in humanized mice, hematopoietic stem cells were isolated from a patient with XIAP deficiency and transplanted to four NOG mice. Three of the four mice showed signs of reconstitution with human immune system components; 0.3-20.4% of PBMC was positive with human-specific anti-CD45 antibody. Two of the three mice were inoculated with EBV and EBV DNA (up to 8×10E+3 copies/μg DNA) was detected in the peripheral blood 6-10 weeks post inoculation. The percentage of CD8+ T cells among peripheral blood lymphocytes increased drastically to ~80% in these mice. These results indicated that humanized mice could be prepared with stem cells isolated from a patient with XIAP deficiency, and EBV can infect these mice and induce CD8+ T cell responses. Peripheral blood levels of human cytokines are currently evaluated to see if hypercytokinemia, characteristic to EBV infection in patients with XIAP deficiency, is reproduced in these mice.
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Report
(3 results)
Research Products
(11 results)
