Abstract
BackgroundThe 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.ResultsWe 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.ConclusionTaken 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.
Highlights
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 involved in physiological processes like embryogenesis and neonatal development, and in a variety of pathophysiological processes, for example atherosclerosis or cancer
Fibroblast growth factor 1 (FGF-1), platelet derived growth factor (PDGF), vascular endothelial growth factor (VEGF) and general serum proteins are capable of activating Egr-1
Since dynamic changes over time cannot be examined by endpoint measurements, studying Egr-1 activity within the living organism could help in gaining new information on in vivo Egr-1 gene activation
Summary
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 involved in physiological processes like embryogenesis and neonatal development, and in a variety of pathophysiological processes, for example atherosclerosis or cancer. Most of the gathered data on Egr-1 gene activation have been evaluated within in vitro studies and could not be confirmed when being re-evaluated in in vivo models [4]. For this reason, it is inevitable to study activation patterns in the living organism over time. Since dynamic changes over time cannot be examined by endpoint measurements, studying Egr-1 activity within the living organism could help in gaining new information on in vivo Egr-1 gene activation
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