Fig. 3.

Early low-dose tamoxifen treatment prolongs survival and improves muscle strength and structure of Mtm1 KO mice. a Photomicrograph of littermates at 28 days of WT, and Mtm1 KO treated with low-dose tamoxifen starting 14 days of age. KO treated with low-dose tamoxifen have normal hindlimb positioning and appear similar in size to WT littermates. b Plots of body weight show that low-dose treated KOs (n = 5) starting at 14 days have similar weight as compared to low-dose treated WT (n = 3) and untreated KOs. c Early TAM treated KOs have improvement in muscle strength when analyzed at 36 and 50 days of age. At 36 days, TAM treated KOs (n = 8) have a mean grip strength of 107 ± 4% vs. TAM treated WT of 100 ± 2% (n = 6, p-value non-significant). At 50 days, TAM treated KOs (n = 4) have a mean grip strength of 95 ± 6% vs. TAM treated WT of 100 ± 4% (n = 3, p-value non-significant). Data normalized to the mean grip strength of WT + TAM littermates. d Early TAM treatment restores Mtm1 KO muscle structure. Cross-sections from tibialis anterior muscle tissue taken at 36 days and stained for H&E, SDH, and dysferlin (scale bars 20 μm). Early TAM treatment improves overall appearance and myofiber size but not % central nuclei. e Myofiber size for KO + TAM = 24 ± 3 μm (n = 3) vs. WT + TAM = 30 ± 4 μm (n = 3, p non-significant). f Average percent of central nuclei (per 100 fibers) in KO + low-dose TAM = 2 ± 0.4% vs. WT + low-dose TAM = 0.2 ± 0.1% (n = 3, *p = 0.03). g Electron microscopy reveals increased triad number in early treated Mtm1 KOs vs. untreated KOs (scale bars 500 nm). However, triad number is decreases as compared to early treated WT. h Quantification of number of triads per field for WT + low-TAM = 19 ± 1.0 (n = 3) vs. KO + low TAM = 10 ± 2.0 (n = 3, *p < 0.02 compared to WT + TAM). For reference, untreated Mtm1 KOs have 5 ± 1.5 (n = 5) (Fig. 3b)