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; 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综合征的特征是颅突变和联合性，主要是由S252W或P253RIN的点突变引起的成纤维细胞生长因子受体（FGFR）2基因。这些突变会根据配体结合而引起FGFR2的激活。最近，APERT综合征小鼠模型（FGFR2敲入小鼠模型）显示出与APERT综合征患者相似的表型。在这项研究中，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，我们通过可溶性FGFR2蛋白或硫酸硫酸盐降解酶对颅内突变症的可溶性FGFR2蛋白或肝素降解酶的影响分析了FGF信号控制的影响，以改善新的非侵入性治疗方法。我们计划并测试了实验，该实验是在纳米凝胶作为局部载体材料作为胎儿时代的小鼠冠状缝合酶操作的硫酸盐降解酶。