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Live in vivo imaging of Egr-1 promoter activity during neonatal development, liver regeneration and wound healing

机译:新生儿发育,肝脏再生和伤口愈合过程中Egr-1启动子活性的活体内成像

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Background The zinc finger transcription factor Egr-1 (Early growth response 1) is central to several growth factors and represents an important activator of target genes not only involved in physiological processes like embryogenesis and neonatal development, but also in a variety of pathophysiological processes, for example atherosclerosis or cancer. Current options to investigate its transcription and activation in vivo are end-point measurements that do not provide insights into dynamic changes in the living organism. Results We developed a transgenic mouse (Egr-1-luc) in which the luciferase reporter gene is under the control of the murine Egr-1 promoter providing a versatile tool to study the time course of Egr-1 activation in vivo. In neonatal mice, bioluminescence imaging revealed a high Egr-1 promoter activity reaching basal levels three weeks after birth with activity at snout, ears and paws. Using a model of partial hepatectomy we could show that Egr-1 promoter activity and Egr-1 mRNA levels were increased in the regenerating liver. In a model of wound healing, we demonstrated that Egr-1 promoter activity was upregulated at the site of injury. Conclusion Taken together, we have developed a transgenic mouse model that allows real time in vivo imaging of the Egr-1 promoter activity. The ability to monitor and quantify Egr-1 activity in the living organism may facilitate a better understanding of Egr-1 function in vivo.
机译:背景技术锌指转录因子Egr-1(早期生长应答1)是几种生长因子的核心,并代表着重要的靶基因激活剂,不仅参与了胚胎发生和新生儿发育等生理过程,而且还参与了多种病理生理过程,例如动脉粥样硬化或癌症。目前在体内研究其转录和激活的选择是终点测量,无法提供对活生物体动态变化的见识。结果我们开发了一种转基因小鼠(Egr-1-luc),其中荧光素酶报道基因在鼠Egr-1启动子的控制下,提供了一种多功能的工具来研究体内Egr-1激活的时间过程。在新生小鼠中,生物发光成像显示高Egr-1启动子活性,在出生后三周达到基础水平,在鼻,耳和爪上具有活性。使用部分肝切除模型,我们可以显示再生肝中Egr-1启动子活性和Egr-1 mRNA水平增加。在伤口愈合的模型中,我们证明了Egr-1启动子活性在损伤部位上调。结论总之,我们已经开发了一种转基因小鼠模型,可以对Egr-1启动子活性进行实时体内成像。监测和定量活生物体中Egr-1活性的能力可能有助于更好地了解体内的Egr-1功能。

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