| Project/Area Number |
16K08713
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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 |
Experimental pathology
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| Research Institution | Nagasaki University |
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Principal Investigator |
KOMATSU Toshimitsu 長崎大学, 医歯薬学総合研究科(医学系), 技術職員 (70380962)
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| Research Collaborator |
SHIMOKAWA Isao
HAYASHI Hiroko
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| Project Period (FY) |
2016-10-21 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | WDR6 / 自己炎症性疾患 / 老化 / カロリー制限 / 代謝 / 寿命 / 遺伝性疾患 |
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| Outline of Final Research Achievements |
Insulin signal is one of the major regulatory signals of aging processes. Previously, we have been reported that WDR6 (WD repeat protein 6) functions as a novel insulin signal molecule. In this research, we analyzed the function of WDR6 using ubiquitous WDR6 KO mice and brain-specific WDR6 KO (bWDR6 KO) mice to reveal the function of WDR6 gene. Unexpectedly, ubiquitous WDR6 KO mice showed autoinflammatory-like symptoms, not aging-symptoms, in adult. Calorie restriction (CR) suppressed the autoinflammatory-like symptoms. It is possible that WDR6 is one of the responsible gene of autoinflammatory. The phenotype of bWDR6 KO mice was normal like that of wild type mice under normal condition. However, the benefit effect of CR in bWDR6 KO mice was attenuated under CR. These results suggest that WDR6 has different roles in tissues.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究によりWDR6の変異が自己炎症性疾患を引き起こす可能性が示された。遺伝性自己炎症性疾患は難病に指定されているものが多く、近年次々と新たな自己炎症性疾患が発見されている。WDR6はまだ未発見の自己炎症性疾患の原因遺伝子である可能性が高く、今後のヒトを含めた更なる解析により自己炎症性疾患の動物モデル構築と治療法開発に期待できる。
脳特異的欠損モデルでは、全身性欠損マウスのような疾患を示さない点、CRの低インスリンなどの特徴的変化を減弱させる点などから、WDR6が組織特異的な機能を有していることを明らかにした。
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