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The Sez12, mouse homolog of DGCR2 gene encoding within 22q11.2, contributes to enchondral ossification in skull base

Research Project

Project/Area Number 16K11460
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Morphological basic dentistry
Research InstitutionTokai University

Principal Investigator

KAJIWARA Kagemasa  東海大学, 医学部, 講師 (00204397)

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)
Research Collaborator ILLINGWORTH Elizabeth  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
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)
KeywordsDGCR2 / 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
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.

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。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (16 results)

All 2018 2017 2016 Other

All Int'l Joint Research (1 results) Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results,  Open Access: 3 results) Presentation (8 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results) Remarks (2 results)

  • [Int'l Joint Research] Prof. Elizabeth Illingworth, Ph.D/Dipartimento di Chimica e Biologia/Universita' degli Studi di Salerno(イタリア)

    • Related Report
      2018 Annual Research Report
  • [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
    • Journal Title

      Journal of Oral and Maxillofacial Surgery

      Volume: 76 (10) Issue: 10 Pages: e71-e72

    • DOI

      10.1016/j.joms.2018.06.152

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The Dgcr2 shows inducible expression and regulates TGF-beta signal activities during hypertrophy of chondrocytes in mouse cranial base synchondrosis2018

    • Author(s)
      Kajiwara, Kagemasa
    • Journal Title

      Journal of Oral Biosciences

      Volume: supplement Pages: 212-212

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Administration of Astragalus Membranaceus prevented kidney dysfunction in mice and in patients with chronic kidney disease2018

    • Author(s)
      Kagemasa Kajiwara, Makoto Arai, Yoshinobu Nakada and Takaaki Kinoue
    • Journal Title

      Nephrology Dialysis Transplantation

      Volume: 33 suppl 1 Issue: suppl_1 Pages: i426-i427

    • DOI

      10.1093/ndt/gfy104.sp247

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Microneedle pH Sensor: Direct, Label-Free, Real-Time Detection of Cerebrospinal Fluid and Bladder pH2017

    • Author(s)
      Ganesh Kumar Mani, Kousei Miyakoda, Asuka Saito, Yutaka Yasoda, Kagemasa Kajiwara, Minoru Kimura, Kazuyosi Tsutiya.
    • Journal Title

      ACS Appl. Mater. Interfaces

      Volume: 9 Issue: 26 Pages: 21651-21659

    • DOI

      10.1021/acsami.7b04225

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Dgcr2 gene contributes to maintenance of chondrocytes in mouse skull base.2017

    • Author(s)
      Kagemasa Kajiwara
    • Journal Title

      Journal of Oral Biosciences

      Volume: Supplement Pages: 196-196

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] Reilly現象が起因となる分子病態メカニズムとその展開2018

    • Author(s)
      梶原景正
    • Organizer
      第6回 日本病巣疾患研究会総会・学術集会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Dgcr2は頭蓋底軟骨結合における肥大軟骨細胞への分化過程でTGF-betaシグナルを抑制性に制御する2018

    • Author(s)
      梶原景正
    • Organizer
      第60回 歯科基礎医学会学術大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 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)
      Kagemasa Kajiwara, Kenichi Aoyama, Masahiro Uchibori, Yoshihide Ota, Minoru Kimura, Kenji Tanigaki and Elisabeth Anne Illingworth
    • Organizer
      100th AAOMS Annual Meeting. Scientific Sessions and Exhibition
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Dgcr2は軟骨内骨化過程における肥大軟骨細胞への分化過程でTGF-betaシグナルを抑制性に制御する2018

    • Author(s)
      梶原景正, 渡部聡, 青山謙一, 内堀雅博, 大澤侑子, 太田嘉英, 木村穣
    • Organizer
      第41回 日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 22q11.2欠失症候群モデルを用いたDgcr2遺伝子による頭蓋底軟骨の制御メカニズムの解析2017

    • Author(s)
      梶原景正
    • Organizer
      第59回歯科基礎医学会学術大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 22q11.2欠失症候群の骨格異常に関するDGCR2のTGF-betaシグナル制御メカニズム2017

    • Author(s)
      梶原景正, 青山謙一, 内堀雅博, 斎藤雅幸, 弥栄聡介, 太田嘉英, 木村穣
    • Organizer
      2017年度生命科学系学会合同年次大会(ConBio2017)
    • Related Report
      2017 Research-status Report
  • [Presentation] 22q11.2欠失症候群の骨格異常に関するDGCR2遺伝子のノックアウトマウスを用いた病因解析2016

    • Author(s)
      梶原 景正, 青山 謙一, 内堀 雅博, 渡部 聡, 金澤 花帆, 太田 嘉英, 木村 穣
    • Organizer
      第39回 日本分子生物学会年会
    • Place of Presentation
      神奈川県 パシフィコ横浜
    • Year and Date
      2016-11-30
    • Related Report
      2016 Research-status Report
  • [Presentation] マウス頭蓋底軟骨結合で発現するDgcr2遺伝子は肥大軟骨細胞のTGF-βシグナルを制御する2016

    • Author(s)
      梶原 景正
    • Organizer
      第58回 歯科基礎医学会学術大会
    • Place of Presentation
      北海道 札幌コンベンションセンター
    • Year and Date
      2016-08-24
    • Related Report
      2016 Research-status Report
  • [Remarks] Kajiwara K. Research Unit

    • URL

      http://kage.med.u-tokai.ac.jp

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
  • [Remarks] Kajiwara, K. research unit

    • URL

      http://kage.med.u-tokai.ac.jp/

    • Related Report
      2016 Research-status Report

URL: 

Published: 2016-04-21   Modified: 2020-03-30  

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