Fig. 4.

Tamoxifen treatment restores triad structure and function in Mtm1 KO mice. a Electron microscopy reveals normal triad structure in WT (arrowheads), reduction of triads in Mtm1 KOs (arrows), and restoration of triads in high-dose TAM treated KOs (arrowheads). Triad number was not improved in low-dose TAM treated KOs (arrows). b Quantification of triad number per field for WT = 17 ± 2 (n = 5), KO = 5 ± 1.5 (n = 5, ****p <0.0001 compared to WT), high-dose TAM treated WT = 14 ± 2 (n = 4), and high-dose TAM treated KOs = 11 ± 2 (n = 5, *p = 0.03 vs. KOs and non-significant vs. WT + TAM). Triad number for low-dose TAM treated KOs = 9.4 ± 5 (n = 4), untreated KOs = 4.8 ± 3 (n = 3, *p < 0.05 compared to WT), WT = 18 ± 5 (n = 3) and WT + low-dose TAM = 20 ± 5 (n = 3). c Calcium transients are increased in dissociated muscle fibers from Mtm1 KO mice treated with high-dose TAM in response to electrically evoked twitch and tetanus stimulation. Representative Mag-Fluo-4 fluorescence traces of FDB fibers during five successive single electrically evoked (Twitch) stimuli and Tetanus (500 ms at 100 Hz) stimulation from either Mtm1 KO, or KO treated with high-dose TAM. d Twitch stimulation is significantly reduced in Mtm1 KOs (0.21 ± 0.01, n = 51 fibers, ****p < 0.0001 vs. WT = 0.38 ± 0.08, n = 73 fibers) and improved with high-dose TAM (0.30 ± 0.01, n = 102 fibers, ****p < 0.0001 vs. KO). e Tetanus stimulation is significantly reduced in KOs compared to WT and improved with high-dose TAM (KO + TAM = 0.60 ± 0.03, n = 103 fibers, ***p < 0.001 vs. untreated KO = 0.40 ± 0.05, n = 51 fibers, ****p < 0.0001 vs. WT = 0.8 ± 0.04, n = 73 fibers, and vs. WT + TAM = 0.70 ± 0.05, n = 53 fibers). Statistical analyses were conducted by two-way ANOVA, followed by Tukey’s multiple comparisons post-test or Fisher’s least common differences post-test. For direct two sample comparisons, unpaired, parametric two-tailed Student's t-test was performed. Scale bars = 500 nm