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

Apert综合征以颅缝闭合和并指畸形为特征，主要由成纤维细胞生长因子受体（FGFR） 2基因S252W或P253Rin点突变引起。这些突变根据配体结合引起FGFR2的激活。最近，一种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。在本研究中，我们计划通过研究Apert综合征小鼠模型的表型来阐明Apert综合征的发病机制。此外，我们还分析了可溶性FGFR2蛋白或硫酸肝素降解酶控制FGF信号对颅缝闭锁的影响，以改进新的无创治疗方法。我们计划并测试了用纳米凝胶作为局部载体材料对胎龄小鼠冠状缝合线进行硫酸肝素降解酶操作的实验。

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.