Fig. 1.

Tamoxifen rescues the phenotype of XLMTM mice. Life-long oral tamoxifen delays disease progression in XLMTM mice. Wild type (WT) and Mtm1^−/y mice were fed control or tamoxifen (TAM)-supplemented diets from weaning onward. a Photographs of WT and Mtm1^−/y mice, illustrating disease severity in young untreated mice and protection conferred by tamoxifen in adult and old mice. b Kaplan–Meier curves showing the effects of treatments on mouse survival. Early death of untreated Mtm1^−/y mice contrasts with prolongation of life span in tamoxifen-treated littermates. Data are from 8 to 18 mice per group. *P ≤ 0.05; ****P ≤ 0.0001. Log-rank (Mantel–Cox) test. c Disease progression was assessed three times per week using a 5-grades clinical scale: muscle function was scored as 1 (normal function of hind limbs), 2 (difficulty in spreading toes), 3 (evident weakness in legs), 4 (paralysis of one hind limb), or 5 (complete paralysis of both legs). WT mice had a clinical score of 1 (normal) throughout the study. Untreated Mtm1^−/y mice quickly reached a high clinical grade, whereas disease progressed much slower in tamoxifen-treated littermates. d Mouse motor function was assessed weekly via a horizontal grid-hanging test. The score of untreated Mtm1^−/y mice declined quickly. Tamoxifen preserved motor function of Mtm1^−/y mice close to WT values. e Mouse body weight was recorded 3 times per week. Tamoxifen affected the growth of WT but not of Mtm1^−/y mice. Mtm1^−/y mice remained smaller than WT mice throughout. b–e Symbols and TAM doses (0.3, 3, and 30 mg kg⁻¹ of diet) are shown on the right-hand side. c, d, e Data represent the mean ± s.e.m. of 8 to 18 mice as defined in a. *P ≤ 0.05; **P ≤ 0.01; ****P ≤ 0.0001; ns non-significant. One-way ANOVA with Fisher’s least significance difference (LSD) post-test