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Dußmann, Philipp (2016): Characterization of a transgenic mouse expressing the reporter gene luciferase under the control of the murine early growth response-1 promoter. Dissertation, LMU München: Medizinische Fakultät



In summary, the present study shows that the observation of luciferase activity, which is congruent with Egr-1-promoter activity over time in the living transgenic Egr-1-luc animal model allows gaining a view of the spatial expression pattern of luc and their changes over time in vivo. The results confirm the ubiquitous role of Egr-1 in proliferation, regeneration, wound healing and development. The present study monitored the Egr-1 activation pattern over time in transgenic mice expressing Egr-1 promoter driven luciferase and showed the spatial expression pattern and their time dependent change in vivo. This transgenic mouse provides a convenient model for studying Egr-1 expression during neonatal development and wound healing at areas were the fur of mice with C57/bl6 background does not interfere with BLI imaging. In neonatal mice, high overall Egr-1 promoter activity was observed, which reached basal levels three weeks after birth with residual activity remaining at snout, ears and paws. In wound healing, Egr-1 promoter activity was highly up regulated at the site of injury. Monitoring Egr-1 activity within internal organs, such as in the liver regeneration model presented, was only possible by endpoint measurements with animals having an opened body cavity. Here it was observed, that Egr-1 promoter activity and Egr-1 mRNA levels were increased in the regenerating liver after partial hepatectomy. In summary, this mouse model allows real time in vivo imaging of Egr-1 promoter activity during development, tissue regeneration and wound healing in vivo and in vitro measurement of Egr-1 promoter activity in SMC cell cultures. To further improve its usability for BLI, crossbreeding into hairless mice will result in a further improvement of its sensitivity by decreasing quenching effects of the fur. Moreover, BLI will then offer a useful tool for monitoring the tissue-specific effects of pharmaceutical drugs over time in vivo, too. This can be especially useful for the development of chemotherapeutic agents binding to certain cancer-specific proteins for example.