Selumetinib from 16 to 20 weeks of age improves skeletal muscle pathology and function in LmnaH222P/H222Pmice. (A) Expression of Myh3 in LmnaH222P/H222P mice measured using real-time quantitative RT-PCR. White bars show relative RNA expression levels in skeletal muscles of DMSO-treated (white bars) and selumetinib-treated (black bars) mice. Values are means ± SEM for n = 5 mice per group; the real time RT-PCR was performed in triplicate with the different RNA sample; *P <0.05. (B) Representative micrographs of hematoxylin and eosin-stained sections of quadriceps from 20-week-old male LmnaH222P/H222P mice (Lmna H222P) treated for 4 weeks with DMSO or selumetinib. Scale bar = 50 mm. Arrows indicate internalized nuclei. To the right of the micrographs, quantitative analyses of muscle fiber diameter (Feret’s diameter) are shown for mice treated with DMSO (circles, solid line) and selumetinib (squares, sold line). Values are means ± SEM for n = 3 mice per group; **P <0.005, ***P <0.0005. (C) Serum CPK activities in LmnaH222P/H222P mice at 16 weeks (16 W) and 20 weeks (20 W) of age that were treated with DMSO (white bars) or selumetinib (black bars). Values are means ± SEM for n = 7 DMSO-treated mice and n = 15 selumetinib-treated mice; **P <0.005, n.s. not significant, #P <0.05. (D) Grip strength (force) in Newtons (N) in LmnaH222P/H222P mice at 20 weeks of age that were treated with DMSO (circles) (n=6) or selumetinib (squares) (n=8). Each circle and square represents a measurement from an individual mouse; the longer horizontal bar are means and the shorter horizontal bars ± SEM; **P <0.05.