In vivo modulation of FGF biological activity alters cranial suture fate
In vivo modulation of FGF biological activity alters cranial suture fate
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DOI：
10.1016/s0002-9440(10)63987-9
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发表时间：
2001-02-01
影响因子：
6
通讯作者：
Longaker, MT
中科院分区：
文献类型：
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作者：
Greenwald, JA;Mehrara, BJ;Longaker, MT
成纤维细胞生长因子受体的功能获得性突变已在许多与颅缝过早融合相关的综合征中被发现。小鼠模型中后额缝在出生后经历程序性融合，而所有其他缝线仍然保持专利状态，为研究控制颅骨缝融合的生物分子机制提供了理想的模型。使用腺病毒载体并在大鼠子宫内注射靶向，我们证明使用显性失活成纤维细胞生长因子受体1构建体可以抑制生理性后额缝融合，而通常专利的冠状缝融合当感染增加碱性成纤维细胞生长因子生物的构建体时融合。活动。我们的数据可能有助于为患有颅缝早闭的儿童开发新颖的、侵入性较小的治疗方案。
Gain-of-function mutations in fibroblast growth factor receptors have been identified in numerous syndromes associated with premature cranial suture fusion. Murine models in which the posterior frontal suture undergoes programmed fusion after birth while all other sutures remain patent provide an ideal model to study the biomolecular mechanisms that govern cranial suture fusion, Using adenoviral vectors and targeted in utero injections in rats, we demonstrate that physiological posterior frontal suture fusion is inhibited using a dominant-negative fibroblast growth factor receptor-1 construct, whereas the normally patent coronal suture fuses when infected with a construct that increases basic fibroblast growth factor biological activity. Our data may facilitate the development of novel, less invasive treatment options for children with craniosynostosis.