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

FGF信号控制治疗Apert综合征颅缝早闭的进展

• 批准号: 24890063
• 负责人: SUZUKI Hiroyuki
• 金额: $ 1.91万
• 依托单位: Tokyo Medical and Dental University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Research Activity Start-up
• 财政年份: 2012
• 资助国家: 日本
• 起止时间: 2012-08-31 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-24890063/
• 关键词: 歯科; 先天異常疾患; 歯学

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.

Apert综合征以颅缝早闭和并指为特征，主要由成纤维细胞生长因子受体（FGFR）2基因S252W或P253R点突变引起。这些突变依赖于配体结合引起FGFR 2的活化。最近，Apert综合征小鼠模型（FGFR2基因敲入小鼠模型）显示出与Apert综合征患者相似的表型，在本研究中，我们计划研究Apert综合征小鼠模型的表型，以阐明Apert综合征的致病机制。此外，我们还分析了可溶性FGFR 2蛋白或肝素硫酸降解酶对FGF信号调控在颅缝早闭中的作用，以改进新的非侵入性治疗方法。我们设计并测试了以纳米凝胶为载体材料在胎龄小鼠冠状缝局部操作硫酸肝素降解酶的实验。

项目成果

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

16例锁骨颅骨发育不良患者牙齿数量及萌出异常的调查

• 发表时间: 2014
• 作者: 鈴木尋之;辻美千子;森田淳平;丸岡亮;鈴木聖一;森山啓司
• 通讯作者: 森山啓司

Supernumerary Teeth and Their Eruption State in Three Siblings with Cleidocranial Dysplasia

锁骨颅骨发育不良三兄妹的多生牙及其萌出状态

• 发表时间: 2012
• 作者: 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
• 通讯作者: 森山啓司