一个4.3 kb的Smad7启动子能够在小鼠发育过程中指定基因表达

Xubao Liu , Qian Chen , Chenzhong Kuang , Meiyu Zhang , Yiwen Ruan , Zao C. Xu , Zhenzhen Wang , Yan Chen
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引用次数: 10

摘要

转化生长因子-β (TGF-β)超家族成员在包括早期发育在内的多种生物学功能中发挥重要作用。这些细胞外因子通过与膜受体相互作用,然后通过一组Smad蛋白进行信号转导来发挥作用。Smad7是一种抑制性Smad蛋白,可特异性拮抗TGF-β和激活素信号。为了表征Smad7的发育作用,我们利用4.3 kb的小鼠Smad7启动子驱动β-半乳糖苷酶的表达,构建了转基因小鼠模型。在这些小鼠中,Smad7启动子以严格调控的时间和空间方式定义了β-半乳糖苷酶的限制性表达模式。在E11.5 ~ E12.5时,β-半乳糖苷酶基因在心脏缓冲组织和大动脉内皮等心血管组织中有短暂表达。通过E12.5 ~ E17.5, β-半乳糖苷酶在发育中的耳蜗上皮和鼻泪管中显著表达。此外,它在三叉神经节、主要关节周围骨骼肌、颌骨原基以及生殖器结节中均有暂时表达。这些研究表明,4.3 kb的Smad7启动子包含足够的调控元件来定义小鼠发育过程中的受控基因表达。
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A 4.3 kb Smad7 promoter is able to specify gene expression during mouse development

Members of transforming growth factor-β (TGF-β) superfamily play important roles in diverse biological functions including early development. These extracellular factors exert their effects by interacting with membrane receptors followed by signal transduction by a group of Smad proteins. Smad7 is an inhibitory Smad protein that specifically antagonizes TGF-β and activin signaling. To characterize the developmental role of Smad7, a transgenic mouse model was generated using a 4.3 kb mouse Smad7 promoter driving β-galactosidase expression. In these mice, the Smad7 promoter defined a restrictive expression pattern of β-galactosidase in a tightly regulated temporal and spatial manner. The β-galactosidase gene was transiently expressed in the cardiovascular structures including heart cushion tissues and the endothelium of major arteries at E11.5 to E12.5. Through E12.5 to E17.5, β-galactosidase expression was prominently detected in the epithelium of developing cochlea and nasolacrimal duct. In addition, it was temporally expressed in trigeminal ganglion, the skeletal muscles surrounding major joints, primordium of the jaws, as well as genital tubercle. These studies indicated that the 4.3 kb Smad7 promoter contains sufficient regulatory elements to define controlled gene expression during mouse development.

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