| Project/Area Number |
18K19642
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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 57:Oral science and related fields
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| Research Institution | Osaka University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
鵜澤 成一 大阪大学, 歯学研究科, 教授 (30345285)
阿部 真土 大阪大学, 歯学研究科, 講師 (40448105)
宇佐美 悠 大阪大学, 歯学研究科, 講師 (80444579)
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| Project Period (FY) |
2018-06-29 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
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| Keywords | 機能亢進型GNAS変異 / 線維性骨異形成症 / floxマウス / GNAS遺伝子変異 / 骨髄間質細胞 / 細胞内シグナル伝達異常 / 細胞内cAMP / 一次シリア / マウスモデル |
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| Outline of Final Research Achievements |
Fibrous dysplasia (FD) is a bone disease that develops when abnormal signal transductions due to GNAS gain-of-function mutations occur in the bone marrow stromal cell etc. In order to elucidate the pathobiology of FD and create FD model that is effective for drug discovery, we created GNAS mutant floppy mice that cause GNAS gain-of-function mutations in target cells when crossed with some Cre mice. When the GNAS mutant floppy mice were crossed with Dmp1-Cre mice expressing Cre in osteocyte/mature osteoblast, GNAS mutant; Dmp1-Cre mice had an increased bone mass, and these changes were compatible with those of GNAS gain-of-function mutations. Therefore, we will be able to create FD model using the GNAS mutant floppy mice.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究の意義は、ヒトの線維性骨異形成症(FD)と全く同じシグナル伝達異常を起こす機能亢進型GNAS変異を目的細胞に誘導できるノックイン（KI)マウスを作製した事にある。KIマウスを用いてFDマウスモデルが作製できれば、ヒトの病態解析と薬効判定をマウスモデルで実施できる。すなわち、このFDマウスモデルから得られた病態情報や創薬シーズは、ヒトのFD治療に有効である。
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