p53 is not necessary for DUX4 pathology

Darko Bosnakovski; Erik A. Toso; Olivia O. Recht; Anja Cucak; Abhinav K Jain; Michelle C. Barton; Michael Kyba

The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. . https://doi.org/10.1101/118315 doi: bioRxiv preprint FSHD. It is possible that at these exceptionally high levels of expression, the p53 pathway does in fact become necessary for some aspect of extreme pathology, however the relevance of such high levels of expression is debatable. The nature of the muscle damage seen in the AAV model is quite distinct from that seen in FSHD, and DUX4 expression is in fact quite difficult to detect in biopsies of FSHD muscle, to the point where the most reliable readout of its expression in biopsies is its target gene fingerprint (Yao et al. 2014 ). It is also theoretically possible that some aspect of the AAV experimental system combines with the effect of DUX4 to make the pathology more severe than it would otherwise have been, and the p53 effect ascribed to DUX4 was in fact downstream of the cellular response to AAV infection.