Figure 1: Mouse model of VML results in irrecoverable loss of function and structure.

(a) VML surgical procedure. From left to right, a photographic sequence shows tattooing and surgical ablation with a micro-blade (indicated by a yellow arrowhead) of a defined mass from a TA muscle. (b) Model of TA muscle with ablation injury. A rendition of the rectangular pocket created within the TA by the surgical excision is shown. (c) Representative H&E staining of whole TA muscle cross-sections. An uninjured TA muscle (left panel) and a TA muscle 30 days following VML injury (right panel) are shown. The tibia and the extensor digitorum longus (EDL) muscle have been drawn for each image to facilitate the orientation and the anatomy of the TA muscles. A dashed line indicates the area corresponding to the muscle area removed in the surgical procedure. For the VML model image, the boxed areas are shown in higher magnification to the right (scale bar=2 mm). Left box: peripheral fibrotic scarring is observed in place of the excised muscle (indicated by arrow bars). Right box: a fibrotic scar can be seen extending into the belly of the TA muscle (indicated by arrow head) (scale bar=500 μm). (d) Quantification of TA muscle tissue masses. TA muscles were weighed immediately following dissection. For muscles subjected to VML injuries, the ablated muscle tissues were immediately weighed (white bar) and added to the muscle mass remaining 30 days after the ablation (red bar). Comparisons were made to unablated muscles. (e) Force production, measured through a force transducer, of TA muscles 30 days after VML injuries compared with uninjured control TA muscles. Contractions were induced in vivo through direct sciatic nerve stimulation (left graph) or ex vivo by inducing contraction directly through electrical stimulation in a culture bath (right graph) (n=6). Data are±s.e.m. For statistical analysis, t-tests were used. *P<0.05; **P<0.001; ****P<0.00001.