2021 Fiscal Year Final Research Report
Elucidation of the onset mechanism of fibrous-osseous lesions in the jawbone caused by TMEM16E mutation
Project/Area Number |
19K10309
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 57060:Surgical dentistry-related
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Research Institution | Hiroshima University |
Principal Investigator |
MIZUTA KUNIKO 広島大学, 医系科学研究科(歯), 助教 (40432679)
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Co-Investigator(Kenkyū-buntansha) |
飛梅 圭 広島大学, 医系科学研究科(歯), 准教授 (40350037)
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Project Period (FY) |
2019-04-01 – 2022-03-31
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Keywords | TMEM16E / ANO5 / GDD |
Outline of Final Research Achievements |
In this study, as a clue to elucidate the molecular mechanism of the onset of TMEM16E-related hereditary diseases, we hypothesized that GDD-type TMEM16E missense mutations produce and accumulate TMEM16E abnormal proteins to develop a bone rare disorder (GDD). Based on this, we have continued to maintain the mouse strain and analyze the phenotype of TMEM16E knock-in mice, and have tried to establish a disease model. However, it was difficult to maintain the strain of the GDD missense mutant TMEM16E knock-in mouse, and no clinical symptoms of GDD could be observed in the knock-in mice.
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Free Research Field |
口腔外科
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Academic Significance and Societal Importance of the Research Achievements |
本研究は,TMEM16E遺伝子の機能および生理的役割を解明することを目的とした. これまでの研究成果から,TMEM16Eに機能獲得型変異がおこると蛋白の安定性獲得による生理機能発揮がGDDを発症させることが予想される.顎骨に生じる線維骨性病変の発症機構は未だ解明されておらず,これを明らかにすることで,その病態の理解と病態に応じた治療法や将来の遺伝子治療の開発が可能になる.TMEM16Eの活性制御が骨の分化および代謝に重要な機能を果たしていることは明らかで,TMEM16Eの機能と安定化調節機構を解明することにより,様々な骨疾患の病態の理解と治療法の開発に役立つことが期待される.
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