Conditional inactivation of FGF receptor 2 reveals an essential role for FGF signaling in the regulation of osteoblast function and bone growth
Conditional inactivation of FGF receptor 2 reveals an essential role for FGF signaling in the regulation of osteoblast function and bone growth
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DOI：
10.1242/dev.00491
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发表时间：
2003-07-01
期刊：
影响因子：
4.6
通讯作者：
Ornitz, DM
中科院分区：
文献类型：
--
作者：
Yu, K;Xu, JS;Ornitz, DM
人颅缝早闭综合征，由成纤维细胞生长因子受体2（FGFR 2）的激活或新形态突变引起，强调了FGFR 2信号传导在骨骼发育中的重要作用。在FGFR 2中携带纯合无效突变的胚胎在骨骼发生之前死亡。为了解决FGFR 2在正常骨发育中的作用，采用了条件性基因缺失方法。同源引入CRE重组酶到Dermo 1（Twist 2）基因位点导致CRE在间充质凝聚中的稳健表达，从而产生成骨细胞和软骨细胞谱系。用Dermo 1-cre灭活floxed Fgfr 2等位基因导致小鼠骨骼侏儒症和骨密度降低。虽然成骨细胞系的分化没有受到干扰，但骨祖细胞的增殖和成熟成骨细胞的合成代谢功能受到严重影响。
Human craniosynostosis syndromes, resulting from activating or neomorphic mutations in fibroblast growth factor receptor 2 (FGFR2), underscore an essential role for FGFR2 signaling in skeletal development. Embryos harboring homozygous null mutations in FGFR2 die prior to skeletogenesis. To address the role of FGFR2 in normal bone development, a conditional gene deletion approach was adopted. Homologous introduction of cre recombinase into the Dermo1 (Twist2) gene locus resulted in robust expression of CRE in mesenchymal condensations giving rise to both osteoblast and chondrocyte lineages. Inactivation of a floxed Fgfr2 allele with Dermo1-cre resulted in mice with skeletal dwarfism and decreased bone density. Although differentiation of the osteoblast lineage was not disturbed, the proliferation of osteoprogenitors and the anabolic function of mature osteoblasts were severely affected.