Figure 5.
Mdm2 dependence of radiosensitivity in p537KR mice. (A) Kaplan-Meier radiation survival curves. WT;Mdm2+/− (n = 9) and p537KR;Mdm2+/− (n = 6) mice under the same genetic background were exposed to 5 Gy whole-body irradiation. Losing one allele of Mdm2 enhanced the radiosensitivity of p537KR mice. P < 0.001. (B) CBC analysis of p537KR;Mdm2+/+ and p537KR;Mdm2+/− mice before irradiation (n = 9) and 2 wk after 5 Gy whole-body irradiation (n = 5) showed severe pancytopenia in p537KR;Mdm2+/− mice. (C) Histopathological evaluation revealed that p537KR;Mdm2+/− mice that died from irradiation exhibited severe atrophy in the spleen and BM. (D) Western analysis of p53 and p21 abundance in spleens isolated from WT, Mdm2+/− (M2+/−), p537KR (7KR), and p537KR;Mdm2+/− (7KR;M2+/−) mice prior to or 3 h after 5 Gy of whole-body irradiation. Actin blot provides a loading control. Intensities of p53 and p21 signals were normalized to Actin signals and are presented as relative fold differences. (E) p537KR;Mdm2+/− mice exhibited a slightly lower frequency of HSC-enriched SLAM cells when compared with p537KR;Mdm2+/+ mice. Error bars represent the SEM from three animals.