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

FSHD muscle [24, [81] [82] [83] [84] 94] . Similarly, the RNA-seq analysis of muscle from the moderate and severe FSHD-like mouse models indicated an enrichment for immune response genes (Figure 7) , and the H&E staining showed mononuclear cell infiltrates after DUX4 induction and the appearance of histopathology (Figures 8 and 9) . Therefore, the mononuclear cell infiltrates The copyright holder for this preprint (which was not peer-reviewed) is the author/funder.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 in gastrocnemius muscles from the moderate ( Figure 14 ) and severe ( Figure 15 ) models were assayed over the time courses of DUX4 induction. Muscle sections were immunostained for CD11b (Itgam, Integrin subunit alpha M), a member of the CD18 integrin family of leukocyte adhesion receptors involved in leukocyte migration [95] , and Ly6g (lymphocyte antigen 6 complex, locus G), a marker for murine neutrophils [96, 97] . Figure 15A -C, respectively). Importantly, these immune phenotypes in the moderate and severe models are consistent with pathology seen in muscles from clinically affected FSHD patients, while the lack of immune cell infiltration in the mild model is consistent with the lack of overt pathology in pre-symptomatic or asymptomatic FSHD subjects.