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

Apert综合征以颅缝融合和并指为特征，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而导致FGFR2的激活。最近，一种Apert综合征小鼠模型(FGFR2敲入小鼠模型)表现出与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综合征的发病机制。此外，我们还分析了通过可溶性FGFR2蛋白或硫酸肝素降解酶调控成纤维细胞生长因子信号在颅缝融合中的作用，以改进新的非侵入性治疗方法。以纳米凝胶为载体材料，在胎龄小鼠的冠状缝线上局部应用硫酸肝素降解酶进行实验研究。

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.