Question: 

The vascular endothelial growth factor receptor (VEGFR-1, flt-1) was shown to play a crucial role in vessel development and different pathologies; in particular it is upregulated and mediates vascularization in the heart during ischemia. Thus, a transgenic mouse model with the live reporter gene eGFP driven by the flt-1 promoter is of high interest.

Methods: 

First, transgenic murine embryonic stem (ES) cells were generated with the help of an flt-1 promoter driven eGFP expression vector. These transgenic ES cells were then used for diploid aggregation to generate transgenic mice.

Results: 

The flt-1/eGFP murine ES cells showed formation of extensive GFP+ vascular networks upon differentiation; endothelial specificity was proven by co-localization with endothelial markers. In transgenic mouse embryos large and small vessels were found to be eGFP+. In contrast, at the adult stage large arteries were eGFP- whereas small vessels were found to be strongly eGFP+ in various organs, e.g. the heart, the lung, the brain and the kidney. In the heart eGFP expression could be detected in small vessels but not in large coronary arteries. When flt-1/eGFP mice were investigated after cryoinfarction we observed extensive remodeling of vascular structures as well as an increase of the endothelial cell area in the peri-infarct zone at 6 days post-injury.

Conclusions: 

The flt-1/eGFP ES cell and mouse model provide useful systems for the monitoring of small vessel formation and remodeling in vitro and in vivo. These models should prove helpful to investigate vascular development and re-vascularization in different organs post-injury.