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

The moderately affected male mice (red line) were assayed prior to TMX injection (D0) and 2, 6, 10, 14, 17, 21, 24 and 28 DPI and compared with age-matched male bi-transgenic mice (green line) and male ACTA1-MCM mice injected with TMX (blue line). C) Severely affected female mice (red line) were assayed prior to TMX injection (D0) and 2, 5, 7, and 8 DPI and compared with age-matched female bi-transgenic mice (green line) and ACTA1-MCM mice injected with TMX (blue line). D) Severely affected male mice (red line) were assayed prior to TMX injection (D0) and 2, 5, 7, and 8 DPI and compared with age-matched male bi-transgenic mice (green line) and ACTA1-MCM mice injected with TMX (blue line). The numbers of mice (n) for each experiment are same as in Figure 4 . Significance = * p<0.05, ** p<0.01, ***p<.001, calculated between bi-transgenic + TMX and bi-transgenic no TMX (green) or ACTA1-MCM + TMX (blue). The copyright holder for this preprint (which was not peer-reviewed) is the author/funder.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 specific maximum twitch force, E) specific maximum tetanus force, and F) specific force frequency. Significance = * p<0.05, ** p<0.01, ***p<.001; blue asterisks indicate significance compared with the ACTA1-MCM control mice and green asterisks indicate significance compared with bi-transgenic MCM;FLExD mild model mice. Levels were normalized to Rpl37 mRNA levels. Significance was calculated using one-way Anova with uncorrected Fisher's LSD. * p<0.05, ** p<0.01, *** p<0.001, ns= not significant Data is plotted as percent fibrotic area. Significance was calculated using the least significant difference test, with *= p<.05, **= p<.01, and ***= p<.001. Figure S9 : Cardiac muscle from FSHD-like mouse models shows no signs of increased fibrosis. Hearts were isolated from the same mice assayed in Figure 14 for skeletal muscle fibrosis. Control ACTA1-MCM mice (blue), bi-transgenic mild model mice (green) and the severe model mice at SD9 (red) show no significant differences in heart fibrosis. The copyright holder for this preprint (which was not peer-reviewed) is the author/funder.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