Fig. 3

Tamoxifen mitigates muscle structure and improves sarcomeric organization in XLMTM mice. Muscle structure and sarcomere ultrastructure were examined by histology and transmission electron microscopy, respectively, in 42-day-old (D42) mice either untreated (control; Ctrl) or treated with tamoxifen (TAM; 30 mg kg⁻¹ of diet). a Representative pictures of hematoxylin–eosin stained sections from the tibialis anterior (TA) of D42 mice. Note the small size of the Mtm1^−/y myofibres and the presence of mislocalized nuclei, a hallmark of Mtm1^−/y mice and XLMTM patients (arrows). b Representative pictures of succinate dehydrogenase (SDH) activity in TA sections of D42 mice, demonstrating abnormal distribution of oxidative staining. The intense staining forming a ring at the periphery of many Mtm1^−/y myofibres (examples shown by asterisks) is due to accumulated mitochondria and other organelles and is a hallmark of the pathology. c The percentage of nuclei abnormally positioned (either internally or centrally located) in TA myofibres of D42 mice were counted from hematoxylin–eosin-stained sections. That feature was reduced by 53.3% with TAM. Data represent the mean ± s.e.m. of n = 2–4 TA per group. ****P ≤ 0.0001. One-way ANOVA followed by Fisher’s LSD post-test. d Sarcomere ultrastructure revealed by transmission electron microscopy in the TA from untreated (control) and tamoxifen-treated Mtm1^−/y mice at D42. Note overall disorganization of the sarcomeres in untreated TA with disruption of the Z-lines (structures running perpendicular to the sarcomeres and holding myofibrils together; arrowheads) and shifted sarcomeres (dashed arrow). Tamoxifen ameliorated the organization of the sarcomeres as demonstrated by in-register Z-lines in adjacent myofibrils (arrowheads). The bar represents 50 µm in a and b, and 2 µm in d