FIGURE 4

Evidence of DNA damage and cellular senescence in GORAB‐deficient cells and bone tissue. (a) Percentage of cells with 53BP1 nuclear foci in GO patient fibroblasts (N = 4). (b) Representative images of nuclear 53 bp1 staining in the secondary spongiosa of proximal tibia in 4 weeks old Gorab^Prx1 mice. Scale bar = 50 μm. (c) Increase in γH2AX expression in femur diaphysis of 4 weeks old Gorab^Prx1 mice (N = 3). (d) Relative expression of Cdkn2a in control and Gorab^Prx1 mice treated with control IgG or 1D11 (N = 5). (e) Representative images and quantitation of senescence associated beta‐galactosidase (SA‐βGal) positive cells in GO patient fibroblasts (N = 4). Scale bar =20 μm. (f) BrdU positive cells in Control and GO patient fibroblasts after 24 h BrdU labeling (N = 4). *p < 0.05, **p < 0.01, ns, no statistically significant difference (unpaired Welch's t‐test).