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

Moderate female mice showed significant declines in fitness 10 days after TMX induction (MD10), dropping from near maximum running times to less than 3 minutes. This decline remained at MD16 before beginning to recover to ~4 min running at MD23 and ~10 min by MD29. In comparison, all male moderate model mice showed a significant decline starting at MD6 (running ~15 min) which progressed more slowly than in females, running for ~10 min at MD10 and ~5 min at MD14 and MD17 before recovering to ~15 min by MD28. Overall, although all moderately affected mice showed significant declines in treadmill fitness over the course of four weeks, female mice were more severely affected and recovered more slowly than male mice. For the severe model mice, female mice declined more rapidly than males, although both showed a significant decline in running time before fatigue, decreasing by over 10 min compared with controls by SD5, a point at which the moderate model mice were still unaffected.