| Project/Area Number |
16K09970
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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 | Saga University |
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Principal Investigator |
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| Research Collaborator |
YOSHIURA koichiro
KINOSHITA akira
MISHIMA hiroyuki
MURATA yuzo
YASAKA toshiharu
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | Sotos症候群 / NSD1 / 学習障害 / モデルマウス / 学習障害モデルマウス |
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| Outline of Final Research Achievements |
In this study, we attempted to establish Sotos syndrome model mice (SoS mice) with learning disability by conditional knockout of Nsd1 gene in the cerebral cortex, hippocampus and olfactory bulb. First, in SoS mice, it was confirmed by RT-PCR that Nsd1 was specifically knocked out in the cerebral cortex and olfactory bulb. In addition, SoS mice showed a low weight until 6 weeks after birth, but showed normal growth thereafter, and both male and female had reproductive ability. Currently, the mice have been backcrossed with C57BL/6J for 6 generations and can now be analyzed. On the other hand, in order to identify the target gene of the Nsd1 protein, we tried to establish the mice in which a 3xTY1 tag was inserted downstream of the Nsd1 gene, but it has not been successful. Further improvement is needed.
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| Academic Significance and Societal Importance of the Research Achievements |
Sotos症候群（SoS)の特徴は、過成長、特異的顔貌、学習障害である。その原因遺伝子は、ヒストンH3リジン36メチル化酵素をコードするNSD1遺伝子であり、そのハプロ不全によって発症する。過去にNSD1のノックアウトマウスが作製されたが、ハプロ不全に相当するヘテロ欠損マウスの表現型は正常であり、一方、ホモ欠損マウスは胚性致死を示した。このように現在のところ、SoSのモデルマウスはない。また、SoSにおいて、QOL上、最も問題となるのは、学習障害である。本研究によるSoS学習障害モデルマウスの樹立は、その発症メカニズムの解明だけでなく、学習障害に対する治療法の開発に役立つと考える。
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