| Project/Area Number |
18K19265
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 42:Veterinary medical science, animal science, and related fields
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| Research Institution | The University of Tokyo |
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Principal Investigator |
Kakuta Shigeru 東京大学, 大学院農学生命科学研究科(農学部), 准教授 (80345032)
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| Co-Investigator(Kenkyū-buntansha) |
小川 哲弘 東京大学, 大学院農学生命科学研究科(農学部), 助教 (40323480)
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| Project Period (FY) |
2018-06-29 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2020: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2018: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | リボヌクレアーゼ / 疾患モデル / マクロファージ / 免疫異常 / 遺伝子欠損マウス / RNA代謝 |
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| Outline of Final Research Achievements |
RNase T2 is a widely conserved endoribonuclease that non-specifically digests single stranded RNA. In humans, it was reported that loss-offunction mutations in the gene encoding RNASET2 lead to congenital cystic leukoencephalopathy. We generated Rnaset2 deficient mice in C57BL/6N background by genome editing. However, immune disorders including splenohepatomegaly, but not neurodegenerative diseases, were developed in Rnaset2 deficient mice. Rnaset2 deficient mice in BALB/cA background were established by backcross, and these mice showed milder phenotypes. In addition, autophagy-visualized Rnaset2 deficient mice were generated, and we found that lack of RNase T2 caused abnormality in autophay processing.
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| Academic Significance and Societal Importance of the Research Achievements |
RNase T2欠損のヒト遺伝病の疾患モデルマウスの樹立を試みたが、残念ながらRNase T2に遺伝子変異を持つマウスはヒトの場合と異なり、神経変性疾患よりも免疫異常の表現型がより強く現れるものであった。すなわち、RNase T2に関連する分子機構には動物種差が存在し、RNase T2の機能解析結果をヒトに外挿する上では、マウスは適切な動物種でないことがわかった。現在はゲノム編集技術により様々な動物種で遺伝子改変が可能となっていることから、より適切な動物種を用いて疾患モデルを作出する必要があると考えられる。
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