MDM2 and neoplasm: To assess the influence Arf expression has on Mdm2 in the absence of overt oncogene overexpression, we generated, and followed for tumor development, p53 heterozygous mice that were Mdm2 wild-type or heterozygous and with only one allele of Arf. Mdm2+/−Arf+/−p53+/− mice had a significantly longer mean survival than Mdm2+/+Arf+/−p53+/− mice (450 versus 376 days, p = 0.0115 log-rank test, Table 1 and Fig. 3).