Fig. 6

GDF11PRO-Fc does not mitigate the dystrophic pathology in mdx mice. 6-week-old mdx mice were treated with AAV9-GDF11PRO-Fc (n = 7), AAV9-GDF11PRO-Fc D122A (n = 7) or vehicle (n = 7) via tail vein injection. Age-matched C57BL/10J (n = 5) mice were also included as a wild type control. Mice were euthanized 12 weeks post-treatment. a Representative HE and MTC staining from gastrocnemius cross-sections of C57BL/10J and mdx mice. Central nucleation is evident in all the mdx groups. Localized areas of myofiber necrosis and regeneration are marked with a black arrow. Fibrotic area is represented by the blue region on MTC staining. Scale bars represent 50 μm in HE sections and 100 μm in MTC sections. b Fibrotic area in the gastrocnemius expressed as a percentage of the total muscle cross-section area. c Percentage of myofibers exhibiting central nucleation. d Measurement of circulating levels of serum CK, a marker of muscle damage. e Representative immunofluorescence images of mouse IgG staining (red) in gastrocnemius tissue cross-sections. Positive staining for IgG indicates myofiber permeability to serum proteins and loss of membrane integrity. Sections were co-stained with WGA to visualize individual myofibers. Zoomed-in area is marked with a white box. Characteristic IgG-positive myofibers are depicted with a white arrow. Scale bars represent 100 μm. f The area of IgG-positive myofibers expressed as a percentage of the total muscle cross-section area. g Representative HE and MTC staining from diaphragm cross-sections of C57BL/10J and mdx mice. Extensive pathology is apparent in mdx but not C57BL/10J mice. Scale bars represent 100 μm. h Fibrotic area in the diaphragm expressed as a percentage of the total cross-section area. *p < 0.05; ***p < 0.001; ****p < 0.0001; n.s. not significant; compared to vehicle-treated mdx controls