| Project/Area Number |
18K15841
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 53020:Cardiology-related
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
Tamura Natsuko 東京医科歯科大学, 大学院医歯学総合研究科, 非常勤講師 (70815597)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 高安動脈炎 / MLX遺伝子 / 褐色脂肪細胞 / クローン病 / MLX / インフラマソーム / オートファジー |
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| Outline of Final Research Achievements |
In this study, we created knock-in mice of the mutant MLX gene revealed by genome-wide association study of patients with Takayasu's arteritis, and aimed to elucidate the pathophysiology by comparing with wild-type mice. Knock-in mice were generated using the CRISPR / Cas9 system. The vascular cross-sectional area of mutant MLX knock-in mice not stimulated by HE staining was significantly increased as compared with wild-type mice of the same week age. The aortic wall was thickened, infiltration of lymphocytes and rupture of elastic fibers were observed, and perivascular lymphadenopathy was observed. It was also characterized by an increase in brown adipose tissue around the aorta, an enlargement of the aortic valve tissue, a thickening of the Peyer's patch of the small intestine, and an enlargement of the smooth muscle of the large intestine.
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| Academic Significance and Societal Importance of the Research Achievements |
高安動脈炎は原因不明の大型血管に発症する血管炎で、主に若年から中年の女性に多い本疾患はアジア人に多いという特徴もあることから、遺伝性疾患が疑われてきた。近年日本で行われたゲノムワイド関連解析で見出された疾患関連遺伝子である、変異型MLX遺伝子を持つマウスを作成し野生型マウスと比較したところ、様々な特徴を捉えることができた。今回の研究成果を足掛かりにしてさらに詳細な病態解明が可能になると考えている。
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