Model cell-line and model animals of MIRAGE syndrome
| Project/Area Number |
15K09599
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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 |
Pediatrics
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| Research Institution | Keio University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
鳴海 覚志 国立研究開発法人国立成育医療研究センター, 分子内分泌研究部, 室長 (40365317)
木下 政人 京都大学, 農学研究科, 助教 (60263125)
石井 智弘 慶應義塾大学, 医学部(信濃町), 准教授 (70265867)
天野 直子 慶應義塾大学, 医学部, 研究員 (70348689)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | MIRAGEs症候群 / 疾患モデル細胞 / 疾患モデル動物 / MIRAGE症候群 / 疾患モデルメダカ / 疾患モデルマウス |
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| Outline of Final Research Achievements |
We first defined MIRAGE ( myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital phenotypes, and enteropathy) syndrome, which is caused by germline de novo hetrozygous SAMD9 mutations. We tested the effect of each SAMD9 protein (wild type or mutant) on the growth of HEK293 cells with inducible expression of these proteins. Expression of the SAMD9 wild-type protein resulted in mild growth restriction, whereas expression of each mutant SAMD9 caused profound growth inhibition. These findings imply that the identified SAMD9 mutations in MIRAGE syndrome activate the intrinsic growth-restricting function of SAMD9 (Nat Genet, 2016). We next generated transgenic mice having Lox P-stop codon-lox P followed by wild-type human SAMD9 gene, which is theoretically driven by ROSA26 gene promoter. These mice, either male or female, are fertile. We are currently generating transgenic medaka having either wild-type or mutant human SAMD9.
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Report
(4 results)
Research Products
(15 results)
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[Presentation] MIRAGE Syndrome: A New Form of Syndromic Adrenal Hypoplasia Caused by Activating SAMD9 Mutations.2016
Author(s)
Narumi S, Amano N, Ishii T, Katsumata N, Fukuzawa R, Shimizu A, Shibata S, Okano H, Miyake N, Matsumoto N, Hasegawa T.
Organizer
The Endocrine Society’s 98th Annual Meeting&Expo
Place of Presentation
Boston, USA
Year and Date
2016-04-01
Related Report
Int'l Joint Research
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