Production of mice and all treatments described were approved by the Institutional Animal Care and Use Committee (IACUC) at Memorial Sloan Kettering Cancer Center (NY), under protocol number 11-06-012. ES cell-derived mice were produced by blastocycst injection by the MSKCC transgenic core facility. Animals were maintained on a mixed C57B6/129 and progeny from breeding were genotyped for specific alleles (R26-rtTA and col1A1) using primers and protocols previously described 17 (link),24 (link). Doxycycline was administered via food pellets (625mg/kg) (Harlan Teklad). Animal studies were not blinded. For detection of p53 protein, animals were sacrificed 4hrs following 6Gy whole body irradiation. For hydrodynamic plasmid delivery 12.5 μg of pCAGs-rtTA3 plasmid was mixed with sterile 0.9% sodium chloride solution. Mice were injected with a total amount of sodium chloride/plasmid mix corresponding to 10 % of the body weight into the lateral tail vein within 5-7 seconds.