Figure 6

Simultaneous MDM2 and p53 tubular cell-specific knockout rescues the pathological phenotype in MDM2/p53^{dKO tubulus} mouse model. (a) Total mRNA was prepared from kidneys isolated from MDM2^{−/−tubulus} /p53^wt/flor MDM2/p53^{dKO tubulus} mice respectively and control MDM2^fl/flmice treated for 11 days with doxycyclin. The target mRNA expression levels were determined by real-time PCR and expressed as mean of the ratio versus the respective 18S mRNA level±S.E.M. (b) Serum creatinine and BUN measurement in plasma of MDM2/p53^{dKO tubulus} and positive control MDM2^{−/−tubulus} /p53^wt/flmice treated for 11 days by doxycycline (n=10 in each group). (c) Kaplan–Meyer survival curve of MDM2/p53^{dKO tubulus} and control MDM2^{−/−tubulus} /p53^wt/flmice (n=10 in each group). (d) Representative images of PAS and p53 stained kidney sections from MDM2/p53^{dKO tubulus} and control MDM2^{−/−tubulus} /p53^wt/flmice treated for 11 days with doxycycline. All images are shown at a magnification of × 200. (e) Real-time PCR analysis of renal tubular damage markers KIM-1, NGAL and TIMP-2 mRNA prepared from kidneys isolated from MDM2/p53^{dKO tubulus} and positive control MDM2^{−/−tubulus} /p53^wt/flmice treated for 11 days with doxycycline. Data are means±S.E.M. ***P<0.005