(A) Moding et al. developed this model (14) using genetically engineered mice in which Atm was selectively deleted in the vast majority of endothelial cells due to transgenic expression of the recombinase Cre from the endothelial-selective VE-cadherin promoter. (B) Subsequently, a sarcoma was induced in these mice. In addition to the alterations of the Atm gene, these mice had p53 flanked by Frt sequences that can be cleaved and deleted by a different recombinase, FlpO. The mice further contained a mutant Kras that is inhibited in its expression by stop sequences that also can be cleaved and deleted by FlpO. Injection of an adenovirus expressing FlpO resulted in expression of oncogenic Kras and loss of p53 and led to sarcoma formation at the site of the injection. Notably, the tumor itself expressed wild-type ATM. (C) Finally, both the tumor and the heart were irradiated, allowing for comparison of tumor endothelial and cardiac endothelial response to radiation.