Fig. 3: Lack of p53 partially rescued the premature death of fortilin^KO-heart mice.

a, b Western blot analyses show that fortilin protein levels were significantly lower in fortilin^KOp53^WT and fortilin^KOp53^KO mice than in fortilin^WTp53^WT mice. p53 protein levels were significantly lower in fortilin^KOp53^KO mice than in fortilin^KOp53^WT mice. c The lack of p53 in the heart of fortilin^KO-heart mice increased the M.S. from 8 to 18 weeks. d, e Echocardiography revealed that the hearts of fortilin^KOp53^KO mice had better overall heart function than those of fortilin^KOp53^WT mice, as evidenced by greater LVEF, less LVIDs (less cavity dilatation), and greater IVSd and LVPWd (less wall thinning). f Immunohistochemistry showed that the lack of p53 drastically reduced the expression levels of both BAX and cleaved lamin, an apoptosis marker. g Western blot analyses showed that the expression levels of BAX, PUMA, and NOXA were significantly decreased when p53 was deleted from fortilin-deficient hearts. a fortilin^WTp53^WT mice (αMHC-Cre^−/−fortilin^flox/floxp53^flox/flox mice), b fortilin^KOp53^WT mice (αMHC-Cre^+/+fortilin^flox/floxp53^WT/WT mice), c fortilin^KOp53^KO mice (αMHC-Cre^+/+fortilin^flox/floxp53^flox/flox mice), IB immunoblot, α-fortilin anti-fortilin antibody, GAPDH glyceraldehyde 3-phosphate dehydrogenase, A.U. arbitrary unit, M.S. median survival, LVEF left ventricular (LV) ejection fraction, LVIDs LV internal diameters in systole, LVIDd LV internal diameters in diastole, LVPWd LV posterior wall thickness in diastole, IVSd interventricular septum thickness in diastole. Scale bar = 200 µm; Error bars, means ± SD, statistical analyses performed using ANOVA with Fisher’s multiple comparison except for the survival assay, for which the Log-Rank (Mantel–Cox) test was used: NS not statistically significant; *P < 0.05; **P < 0.01; ***P < 0.005, ****P < 0.001 (see also Figs. S2 and S3).