Fig. 3

HDAC inhibitors improve phenotypic outcomes in Mtm1 KO mice. a, b Valproic acid (VPA) treatment starting at 21 days promotes significant improvement in Mtm1 KO survival [median survival 65 days (n?=?5) vs. 45 days for Mtm1 KOs?+?PBS (n?=?5), **p?<?0.01]. VPA improves strength as measured by wire hang duration (n?=?2?4 per timepoint; best-fit curves by least squares regression are different, p?=?0.0002). c, d Trichostatin A (TSA) has a measurable, yet much less positive, effect on KO mice. TSA treatment starting at 21 days promotes significant improvement in Mtm1 KO survival [median survival 50 days (n?=?10) vs. 45 days for Mtm1 KOs?+?DMSO (n?=?11), *p?<?0.05]. TSA improves strength as measured by wire hang duration (n?=?2?11 per timepoint; best-fit curves by least squares regression are different, p?<?0.001). e, f Tibialis anterior muscle cross-sections at 35 days stained with haematoxylin and eosin (scale bar?=?20 µm). VPA treatment is associated with a reduction in number of centrally nucleated fibres that is not significant. From left to right, Mean % central nuclei?±?SEM are 0.17?±?0.11%, 0.15?±?0.07%, 5.20?±?0.95%, 2.40?±?0.32%; n?=?1836, 2069, 6983, 6167 total fibres counted across 6?10 different fields from n?=?5 to 6 animals; Kruskal?Wallis test with Dunn?s post-test; **p?<?0.01. g VPA treatment significantly improves myofiber diameter size in Mtm1 KO mice as measured by minimum Feret?s diameter. From left to right, Mean Feret?s diameter?±?S.E.M are: 45.54?±?0.388, 42.16?±?0.332, 21.39?±?0.185, 25.39?±?0.224, respectively. From left to right, % myofiber size distribution for?<?10 ?m/10?20 ?m/20?30 ?m/30?40 ?m/?>?40 ?m bins are: 0/0.497/11.019/26.678/61.806; 0.0633/1.456/16.835/30.380/51.266; 8.358/41.605/36.119/8.873/5.044; 3.033/33.037/37.323/15.326/11.282; n?=?1207, 1580, 2716, 2473 total fibers measured across three different sections from n?=?5?6 animals; Kruskal?Wallis test with Dunn?s post-test; ***p?<?0.001