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Research strategy for identification of the pathogenesis of the common structural abnormalies in craniomaxillofacial region

Research Project

Project/Area Number 26293436
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Orthodontics/Pediatric dentistry
Research InstitutionThe University of Tokushima

Principal Investigator

TANAKA Eiji  徳島大学, 大学院医歯薬学研究部, 教授 (40273693)

Co-Investigator(Kenkyū-buntansha) 井本 逸勢 (井本 逸勢(橘逸勢))  徳島大学, 大学院医歯薬学研究部, 教授 (30258610)
泰江 章博  徳島大学, 大学病院, 講師 (80380046)
Research Collaborator MITSUI Naomi  徳島大学, 大学院医歯薬学研究部, ポスドク
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥16,250,000 (Direct Cost: ¥12,500,000、Indirect Cost: ¥3,750,000)
Fiscal Year 2016: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2015: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
Keywordsゲノム編集 / 遺伝子疾患 / CRISPR/Cas / 非症候性多数歯欠損 / TALEN / 突然変異導入
Outline of Final Research Achievements

Non-syndromic tooth agenesis has been associated with mutation in a variety of genes involved in tooth morphogenesis. We identified a novel frameshift mutation of the highly conserved C-terminal domain of MSX1, known as Msx homology domain 6 (MH6), in a Japanese family with non-syndromic tooth agenesis. To investigate the importance of MH6 in tooth development, Msx1 was targeted in mice with a CRISPR/Cas system. Although heterozygous MH6 disruption did not alter normal craniofacial development, homozygous mice exhibited agenesis of lower incisors with or without cleft palate at E16.5. In addition, agenesis of the upper third molars and the lower second and third molars were observed in 4-week-old mutant mice. Although the upper second molars were present, they were abnormally small. These results suggest that the C-terminal domain of MSX1 is important for tooth and palate development.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • Research Products

    (23 results)

All 2017 2016 2015 2014

All Journal Article (12 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 12 results,  Acknowledgement Compliant: 9 results,  Open Access: 8 results) Presentation (11 results) (of which Int'l Joint Research: 3 results,  Invited: 1 results)

  • [Journal Article] Roles of hypoxia inducible factor-1α in the temporomandibular joint2017

    • Author(s)
      Mino-Oka A, Izawa T, Shinohara T, Mori H, Yasue A, Tomita S, Tanaka E
    • Journal Title

      Archives of Oral Biology

      Volume: 73(1) Pages: 274-281

    • DOI

      10.1016/j.archoralbio.2016.10.028

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Relationship between somatic mosaicism of Pax6 mutation and variable developmental eye abnormalities-an analysis of CRISPR genome-edited mouse embryos.2017

    • Author(s)
      Yasue A, Kono H, Habuta M, Bando T, Sato K, Inoue J, Oyadomari S, Noji S, Tanaka E, Ohuchi H.
    • Journal Title

      Sci Rep

      Volume: 7 Issue: 1 Pages: 53-53

    • DOI

      10.1038/s41598-017-00088-w

    • NAID

      120006534995

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Dynamic and stress relaxation properties of the whole porcine temporomandibular joint disc under compression2016

    • Author(s)
      Barrientos E, Pelayo F, Tanaka E, Lamela-Rey MJ, Fernandez-Canteli A
    • Journal Title

      Journal of Mechanical Behaior of Biomedical Materials

      Volume: 57 Pages: 109-115

    • DOI

      10.1016/j.jmbbm.2017.03.035

    • NAID

      120006797816

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] The nuclear receptor AhR controls bone homeostasis by regulating osteoclast differentiation via the RANK/c-Fos signaling axis.2016

    • Author(s)
      Izawa T, Arakaki R, Mori H, Tsunematsu T, Kudo Y, Tanaka E, Ishimaru N
    • Journal Title

      Journal of Immunology

      Volume: 197 Pages: 4639-4650

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Hyaluronan metabolism in overloaded temporomandibular joint.2016

    • Author(s)
      Shinohara T, Izawa T, Mino-Oka A, Mori H, Iwasa A, Inubushi T, Yamaguchi Y, Tanaka E
    • Journal Title

      Journal of Oral Rehabilitation

      Volume: 43 Issue: 12 Pages: 921-928

    • DOI

      10.1111/joor.12443

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] The Effectiveness of Human Parathyroid Hormone and Low-Intensity Pulsed Ultrasound on the Fracture Healing in Osteoporotic Bones.2016

    • Author(s)
      Mansjur KQ, Kuroda S, Izawa T, Maeda Y, Sato M, Watanabe K, Horiuchi S, Tanaka E.
    • Journal Title

      Annals of Biomedical Engineering

      Volume: 印刷中 Issue: 8 Pages: 2480-2488

    • DOI

      10.1007/s10439-015-1533-y

    • Related Report
      2016 Annual Research Report 2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Novel human mutation and CRISPR/Cas genome-edited mice reveal importance of C-terminal domain of MSX1 in tooth and palate development2016

    • Author(s)
      S.N.Mitsui, A.Yasue, K.Masuda, T.Naruto, Y.Minegishi, S.Oyadomari, S.Noji, I.Imoto, E.Tanaka
    • Journal Title

      Scientific Reports

      Volume: 6 Issue: 1 Pages: 38398-38398

    • DOI

      10.1038/srep38398

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Rebamipide attenuates mandibular condylar degeneration in a murine model of TMJ-OA by mediating a chondroprotective effect and by downregulating RANKL-mediated osteoclastogenesis.2016

    • Author(s)
      Izawa T, Mori H, Shinohara T, Mino A, Hutami IR, Iwasa A, TanakaE.
    • Journal Title

      PLoS ONE

      Volume: 印刷中

    • NAID

      120006534950

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Dynamic and stress relaxation properties of the whole porcine temporomandibular joint disc under compression.2016

    • Author(s)
      Barrientos E, Pelayo F, Tanaka E, Lamela-Rey MJ, Fernandez-Canteli A
    • Journal Title

      Journal of Mechanical Behavior & Biomedical Materials

      Volume: 57 Pages: 109-115

    • NAID

      120006797816

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Smad3 decifiency leads to mandibular condyle degradation via the Sphingosine 1-phosphate (S1P) / S1P3 signaling axis.2015

    • Author(s)
      Mori H, Izawa T, Tanaka E
    • Journal Title

      American Journal of Pathology

      Volume: 185 Pages: 2742-2756

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Low-intensity pulsed ultrasound rescues insufficient salivary secretion in autoimmune sialadenitis.2015

    • Author(s)
      Sato M, Kuroda S, Mansjur KQ, Ganzorig K, Nagata K, Horiuchi S, Inubushi T, Yamamura Y, Azuma M, Tanaka E
    • Journal Title

      Arthritis Research & Therapy

      Volume: 17 Issue: 1 Pages: 278-278

    • DOI

      10.1186/s13075-015-0798-8

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Highly efficient targeted mutagenesis in one-cell mouse embryos mediated by the TALEN and CRISPR/Cas systems2014

    • Author(s)
      A. Yasue, S. N. Mitsui, T. Watanabe, T. Sakuma, S. Oyadomari, T. Yamamoto, S. Noji, T. Mito and E. Tanaka
    • Journal Title

      Sci Rep

      Volume: 4 Issue: 1 Pages: 5705-5705

    • DOI

      10.1038/srep05705

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Rogdi Disrupted Mice Showed Amelogenesis Imperfecta-like Phenotype2017

    • Author(s)
      Silvia Mitsui Naomi, Akihiro Yasue, Shinya Horiuchi, Seiichi Oyadomari, Eiji Tanaka
    • Organizer
      第95回国際歯科研究学会(IADR)
    • Place of Presentation
      San Francisco(米国)
    • Year and Date
      2017-03-23
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Biological validation of tooth agenesis causing mutation using CRISPR/Cas system in mice.2016

    • Author(s)
      Naomi Mitsui, Akihiro Yasue, Issei Imoto, Seiichi Oyadomari, Eiji Tanaka
    • Organizer
      第75回日本矯正歯科学会
    • Place of Presentation
      アスティとくしま(徳島県徳島市)
    • Year and Date
      2016-11-08
    • Related Report
      2016 Annual Research Report
  • [Presentation] HIF-1α+/-マウスを用いた変形性顎関節症におけるHIF-1αの機能解析.2016

    • Author(s)
      岡 彰子、井澤 俊、篠原丈裕、森 浩喜、田中栄二
    • Organizer
      第29回日本顎関節学会総会
    • Place of Presentation
      湯本富士屋ホテル(神奈川県足柄下郡)
    • Year and Date
      2016-07-17
    • Related Report
      2016 Annual Research Report
  • [Presentation] Low-intensity pulsed ultrasound rescues insufficient salivary secretion in Sjogren syndrome.2016

    • Author(s)
      Sato M, Mansjur KQ, Tanaka E
    • Organizer
      AADR/CADR Annual Meeting & Exhibition
    • Place of Presentation
      Los Angels, CA, USA
    • Year and Date
      2016-03-16
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Combined therapeutic effects of parathyroid hormone and low-intensity pulsed ultrasound enhance bone fracture healing in osteoporotic rats.2016

    • Author(s)
      Mansjur KQ, Sato M, Tanaka E
    • Organizer
      AADR/CADR Annual Meeting & Exhibition
    • Place of Presentation
      Los Angels, CA, USA
    • Year and Date
      2016-03-16
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ゲノム編集技術を用いたマウス1細胞期胚における遺伝子変異導入.2016

    • Author(s)
      泰江章博、田中栄二
    • Organizer
      平成27年度革新的特色研究シンポジウム「エピゲノムと臓器ネットワークで迫る次世代糖尿病研究」
    • Place of Presentation
      徳島大学藤井節郎記念ホール(徳島県徳島市)
    • Year and Date
      2016-02-08
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Study of Pax6-deficient mosaic mice generated by the CRISPR/Cas system.2015

    • Author(s)
      Akihiro Yasue, Hitomi Kono, Tetsuya Bando, Yoshiyasu Ishimaru, Junji Inoue, Takahiro Watanabe, Seiichi Oyadomari, Sumihare Noji, Taro Mito, Hideyo Ohuchi, Eiji Tanaka
    • Organizer
      第48回日本発生生物学会
    • Place of Presentation
      つくば国際会議場(茨城県つくば市)
    • Year and Date
      2015-06-02
    • Related Report
      2015 Annual Research Report
  • [Presentation] Mutation affecting the C-terminal of MSX1 causes non-syndromic tooth agenesis2015

    • Author(s)
      Mitsui SN, Yasue A, Tanaka E
    • Organizer
      93rd IADR
    • Place of Presentation
      Boston, CA, USA
    • Year and Date
      2015-03-08 – 2015-03-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] Sequence analysis and in vitro study of novel mutations identified in patients with tooth agenesis2014

    • Author(s)
      Mitsui SN, Yasue A, Matsuda K, Watanabe K, Horiuchi S, Imoto I, Tanaka E
    • Organizer
      The 3rd ASEAN Plus and Tokushima Joint International Conference
    • Place of Presentation
      Makassar, Indonesia
    • Year and Date
      2014-12-05
    • Related Report
      2014 Annual Research Report
  • [Presentation] CRISPR/CasシステムによるPax6遺伝子破壊マウスの解析2014

    • Author(s)
      河野仁美、泰江章博、石丸善康、井上順治、渡辺崇仁、板東哲哉、親泊政一、野地澄晴、三戸太郎、山本卓、田中栄二、大内淑代
    • Organizer
      第37回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜, 神奈川県横浜市
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] Highly efficient targeted mutagenesis in one-cell mouse embryos mediated by TALEN and CRISPR/Cas systems2014

    • Author(s)
      Yasue A, Mitsui SN, Watanabe T, Sakuma T, Oyadomari S, Yamamoto T, Noji S, Mito T, Tanaka E
    • Organizer
      X meeting for Spanish Society for Developmental Biology (SEBD)
    • Place of Presentation
      Madrid, Spain
    • Year and Date
      2014-10-13 – 2014-10-15
    • Related Report
      2014 Annual Research Report

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Published: 2014-04-04   Modified: 2018-03-22  

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