Project/Area Number |
16K20240
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
Otorhinolaryngology
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Research Institution | Nagoya University |
Principal Investigator |
YOSHIDA TADAO 名古屋大学, 医学部附属病院, 講師 (90567017)
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Project Period (FY) |
2016-04-01 – 2020-03-31
|
Project Status |
Completed (Fiscal Year 2019)
|
Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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Keywords | MYH9異常症 / R702C / ノックインマウス / 難聴 / MYH9異常症モデルマウス / 内耳障害 / 遺伝子 / 応用動物 |
Outline of Final Research Achievements |
The results of ABR in R702C-Atoth1 mice revealed that some mice caused hearing loss and others did not. Three out of 46 mice showed 70 dB or more in all frequency ranges. Immunostaining was performed using NMMHC-IIA (MYH9). A negative control was prepared. The expression site of the NMMHC-IIA in the inner ear was compared in three individuals in one wild-type gene expression and two expressing the deafness in the R702C-Atoth1 mice. As shown in FIGS. 2 and 3, the expression was almost the same as that of the wild type, and there was no difference between individuals. No morphological changes were observed on light microscopy and immunostaining. Since only a very small amount of the inner ear tissue sample can be obtained, the amount was insufficient to confirm that the MYH R702C gene was contained in the inner ear in a tissue-specific manner. In the future, we will focus on the morphological change of sensory hair, which is a finer structure, and study it repeatedly.
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Academic Significance and Societal Importance of the Research Achievements |
R702Cノックインマウスを用いて、非筋ミオシン重鎖IIAを介した難聴の発症機構を解明するという仮説のもと本研究を行った。実際には、ノックインマウスを用いて、致死率が低く、内耳特異的に遺伝子を発現するマウスの作成を試みて、内耳組織の検討を行った。結果として表現型としての難聴を示すマウスが少なかったため、遺伝子が内耳に導入されにくいのか、導入されても表現型として難聴を示さないのかは鑑別が困難であった。これは内耳の組織が非常に小さく遺伝子が特異的に導入されているか検査を行うことが困難であったからである。今後、内耳への遺伝子導入を確認する手法の確立が期待される。
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