Transgenic mice expressing tunable levels of DUX4 develop characteristic facioscapulohumeral muscular dystrophy-like pathophysiology ranging in severity

Takako I. Jones; Guo-Liang Chew; Pamela Barraza-Flores; Spencer Schreier; Monique Ramirez; Ryan D. Wuebbles; Dean J. Burkin; Robert K. Bradley; Peter L. Jones

Therefore, cross sections of the TA muscles isolated from the above series of control, mild, moderate, and severe FSHD-like mice were assayed for the extent of fibrosis developing over time using SR staining (Figures 16, S8, and S9 ). The muscles from control ACTA1-MCM/+ and mild bi-transgenic model had similar low levels (~2% fibrotic area) of fibrosis (Figure 16A , F, G, and Figure S8 ). The moderate bi-transgenic model had similar control levels of fibrosis at MD3 and MD6; however, this model showed a small but significant 50% increase in fibrosis by MD14 and MD28 ( Figure 16B -E and Figure S8 ). The severe bi-transgenic model showed increased fibrosis by SD3 and a maximal 2.5-fold increase in fibrosis (5.5% fibrotic area) at SD9 . CC-BY-NC 4.0 International license is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It . https://doi.org/10.1101/471094 doi: bioRxiv preprint ( Figure 16 H-J, and Figure S8 ). The heart, which does not express detectable DUX4-fl in any of the models, showed no signs of fibrosis ( Figure S9 ).