FIGURE 5.
DUX4 causes apoptosis through a p53-dependent mechanism. (A) DUX4-induced apoptosis is significantly reduced by Bax, p53, or caspase-1 inhibition, in vitro. **p < 0.01; ***p < 0.001 (analysis of variance). RFU = relative fluorescent units from caspase-3/7 assay. (B) V5 immunofluorescence and DAPI staining showed DUX4 expression in Trp53 −/− mouse myonuclei 2 weeks after injection. Scale bar = 50mm. (C) Trp53 −/− muscles are resistant to DUX4-induced degeneration, indicated by normal muscle histology in DUX4-transduced muscles, 2 weeks postinjection. In contrast, low-dose AAV6.DUX4 (8 × 108 DRP) caused massive myofiber degeneration and subsequent regeneration 2 weeks postinjection. Scale bar = 500mm.