Development of therapy for craniosynostosis in Apert syndrome by FGF signal control

• Project/Area Number: 24890063
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Orthodontic/Pediatric dentistry
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: SUZUKI Hiroyuki 東京医科歯科大学, 硬組織疾患ゲノムセンター, 特任助教 (70634492)
• Project Period (FY): 2012-08-31 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 歯科 / 先天異常疾患 / 歯学

Research Abstract

Apert syndrome is characterized by craniosynostosis and syndactyly, and is predominantly caused by point mutation of either S252W or P253Rin the fibroblast growth factor receptor (FGFR) 2 gene. These mutation cause activation of FGFR2 depending on ligand binding. Recently, an Apert syndrome mouse model(FGFR2 knock-in mouse model) showed phenotypes similar to those of Apert syndrome patients.
In this study, we plan to investigate the phenotypes of Apert syndrome mouse model to clarify the pathogenic mechanism of Apert syndrome. Moreover, we analyze the effects of FGF signal control by soluble FGFR2 protein or heparin sulfate-degrading enzyme on craniosynostosis to improve new noninvasive therapeutic approach. We planed and tested the experiment that we operated heparin sulfate-degrading enzyme on coronal suture of mouse at a fetal age by nanogel as a carrier material locally.

Research Products

• [Journal Article] ADAMTSL6ss rescues fibrillin-1 microfibril disorder in Marfan syndrome mouse model through the promotion of fibrillin-1 assembly (2011)
  • Author(s): Saito M, Kurokawa M, Oda M, Oshima M, Tsutsui K, Kosaka K, Nakao K, Ogawa M, Manabe RI, Suda N, Ganjargal G, Hada Y, Noguchi T, Teranaka T, Sekiguchi K, Yoneda T, Tsuji T
  • Journal Title: J Biol Chem Volume: 286 Issue: 9 Pages: 38602-13
  • DOI: 10.1002/jcp.24021
  • Peer Reviewed
• [Presentation] 鎖骨頭蓋異形成症16例における歯数および萌出の異常に関しての検討 (2014)
  • Author(s): 鈴木尋之、辻美千子、森田淳平、丸岡亮、鈴木聖一、森山啓司
  • Organizer: 第54回日本先天異常学会学術集会
  • Place of Presentation: 神奈川県(日本)(発表予定)
  • Year and Date: 2014-07-26
• [Presentation] 鎖骨頭蓋異形成症16例における歯数および萌出の異常に関しての検討 (2014)
  • Author(s): 鈴木 尋之
  • Organizer: 第54回日本先天異常学会学術集会
  • Place of Presentation: 麻布大学（神奈川県、日本）
• [Presentation] Supernumerary Teeth and Their Eruption State in Three Siblings with Cleidocranial Dysplasia (2012)
  • Author(s): 鈴木尋之、辻美千子、志賀百年、岡村絵里花、鈴木聖一、森山啓司
  • Organizer: The 45th Annual Scientific Congress of Korean Association of Orthodontists
  • Place of Presentation: ソウル(大韓民国)
  • Year and Date: 2012-11-01
• [Presentation] Supernumerary Teeth and Their Eruption State in Three Siblings with Cleidocranial Dysplasia (2012)
  • Author(s): 鈴木 尋之
  • Organizer: The 45th Annual Scientific Congress of Korean Association of Orthodontists
  • Place of Presentation: ソウル（大韓民国）