The Sez12, mouse homolog of DGCR2 gene encoding within 22q11.2, contributes to enchondral ossification in skull base
| Project/Area Number |
16K11460
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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 |
Morphological basic dentistry
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| Research Institution | Tokai University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
木村 穣 東海大学, 医学部, 教授 (10146706)
青山 謙一 東海大学, 医学部, 助教 (10647530)
内堀 雅博 東海大学, 医学部, 助教 (50749273)
太田 嘉英 東海大学, 医学部, 教授 (60233152)
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| Research Collaborator |
ILLINGWORTH Elizabeth
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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 |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | DGCR2 / 22q11.2欠失症候群 / 頭蓋底軟骨結合 / 肥大軟骨細胞 / ノックアウトマウス / Sez12 / Tbx1 / Df1 / Dgcr2 / 初代培養軟骨細胞 / X型コラーゲン / TGF-betaシグナル / TBX1 / 初代軟骨細胞 / TGF-beta / DGCR2遺伝子 / 軟骨細胞 / BMP / 顎顔面形態形成 / Dgcr2ノックアウトマウス / 遺伝子解析 |
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| Outline of Final Research Achievements |
We examined whether the DGCR2, human homolog of Sez12, plays a candidate for pathological severity of 22q11.2 deletion syndrome. We generated Sez12 knockout/EGFP-knockin (Sez12-KO) mice. After weaning, half of Sez12-KO mice showed mild skeletal abnormalities with flat face. Skeletal analyses revealed maxillofacial dysplasia caused by earlier defect of synchondrodial joint in Sez12-KO mice. The skull base showed abnormalities in enchondral ossification, especially in hypertrophic chondrocytes. The knock-in EGFP was expressed in the decreased hypertrophic chondrocytes in Sez12-KO mice. However, heterozygous Sez12-KO mice showed no phenotype. We generated a heterozygous mutant for both Sez12 and Tbx1 (double hetero mice). As well as the Sez12-KO, the double hetero mice showed maxillofacial abnormalities caused by defects in enchondral ossification, suggesting Sez12 together with Tbx1 and molecule(s) expressed within 22q11.2 play an important role in maxillofacial development.
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| Academic Significance and Societal Importance of the Research Achievements |
22q11.2欠失症候群の診断では顔貌異常が重要な所見となり、その分子メカニズムを解明することは学術的意義がある。また通常は悪性腫瘍細胞でのみ発現するといわれたTGF-betaシグナル阻害機能が、軟骨細胞分化過程でSez12遺伝子機能として発現し、軟骨内骨化に重要な役割を果たしていることも学術的意義がある。Sez12遺伝子機能で発揮される頭蓋底軟骨の軟骨内骨化への影響が生後個体でのみ認められることは、生後の患者を対象とした顎顔面領域への臨床的応用に期待がかかり、社会的意義は大きい。
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Report
(4 results)
Research Products
(16 results)
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[Journal Article] The mouse homolog of DGCR2 gene encoding within 22q11.2 contributes to enchondral ossification in skull base and its defect causes the severity in 22q11.2 deletion syndrome2018
Author(s)
Kajiwara, K., Aoyama, K., Uchibori, M., Ota, Y., Kimura, M., Tanigaki, K. and Elizabeth Illingworth
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Journal Title
Journal of Oral and Maxillofacial Surgery
Volume: 76 (10)
Issue: 10
Pages: e71-e72
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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