CM telomere dysfunction induces cell-cycle arrest through p21 activation. (A) Relative p21 gene expression measured by quantitative PCR. n indicates the number of animals analyzed. Cryo, cryoinjury at P1 analyzed at 7 dpi (at P8). (B) Detail of p21 and TnI immunofluorescence at P1. Arrowheads indicate p21-positive CMs. Bars, 50 µm. (C) Quantification of p21-positive CMs at P1. n indicates the number of animals analyzed. (D) Detail of p21 and TnI immunofluorescence analyzed 7 dpi at P1. Controls are age-matched uninjured animals. Arrowheads indicate p21-positive CMs. Bars, 50 µm. (E) Quantification of p21-positive CMs 7 dpi at P1. n indicates the number of animals analyzed. (F) Detail of pH3 and TnT immunofluorescence in WT and p21^−/− mice analyzed 7 dpi at P7. Arrowheads indicate mitotic CMs. Bars, 100 µm. (G) Quantification of the number of CMs in mitosis in WT and p21^−/− mice analyzed 7 dpi at P7. n indicates the number of animals analyzed. (H) Representative Masson’s trichrome staining in WT and p21^−/− hearts cryoinjured at P7 and analyzed 28 dpi. Bars, 1 mm. (I) Quantification of fibrotic area in WT and p21^−/− hearts cryoinjured at P7 and analyzed 28 dpi. n indicates the number of animals analyzed. (J) Number of CMs in mitosis in WT, G3 Terc^−/−, G3 Terc^−/−/p21^−/−, and p21^−/− mice at P1. n indicates the number of animals analyzed. (K) Number of CMs in mitosis in WT, G3 Terc^−/−, and G3 Terc^−/−/p21^−/− mice cryoinjured at P1 and analyzed at 7 dpi. n indicates the number of animals analyzed. Data are mean ± SEM. *, P < 0.05; **, P < 0.01; ***, P < 0.001; NS, non-significant.