Alleviated NMJ deficits in HSA-Lmna−/− mice by rapsyn expression. A, Overexpression of rapsyn in TA muscles of 2 M Rapsyn-Tg mice. B, Elevated rapsyn protein in HSA-Lmna−/−; Rapsyn-Tg muscles. C, Quantitative analysis for data in B. Data were shown as mean ± SEM. Lmnaf^f/f versus HSA-Lmna−/−, t₍₄₎ = 11.44, ***p = 0.0003; HSA-Lmna−/− versus HSA-Lmna−/−; Rapsyn-Tg, t₍₄₎ = 2.822, *p = 0.0477. Unpaired t test, n = 3 mice per group. D, Improved NMJ morphologic deficits in HSA-Lmna−/− mice by rapsyn expression. Top, TA muscles of mice from different ages and indicated genotypes were whole-mount stained with CF568 α-BTX (red) and anti-NF/Syn antibodies (green). Blue arrowhead, denervated or partially innervated NMJ. Scale bar, 50 µm. Bottom, Enlarged images of individual NMJ. Scale bar, 20 µm. E–G, Quantitative analysis of data in D. E, Rescue of NMJ denervation in HSA-Lmna−/− mice by rapsyn expression. F_(2,12) = 62.32, ***p < 0.0001 for Lmna^f/f versus HSA-Lmna−/−; **p = 0.0013 for HSA-Lmna−/−; Rapsyn-Tg versus HSA-Lmna−/−. F, Rescue of fragmentation in HSA-Lmna−/− mice by rapsyn expression. F_(2,12) = 31.41, ***p < 0.0001 for Lmna^f/f versus HSA-Lmna−/−; **p = 0.0040 for HSA-Lmna−/−; Rapsyn-Tg versus HSA-Lmna−/−. G, Rescue of reduced AChR cluster area in HSA-Lmna−/− mice by rapsyn expression. F_(2,12) = 10.39, **p = 0.0045 for Lmna^f/f versus HSA-Lmna−/−; *p = 0.0115 for HSA-Lmna−/−; Rapsyn-Tg versus HSA-Lmna−/−. Data were shown as mean ± SEM, one-way ANOVA with Tukey's multiple comparison test, n = 5 mice per genotype. H–J, Increased CMAP amplitudes of HSA-Lmna−/− mice by rapsyn expression. H, Representative CMAP traces at 40-Hz stimulations. I, Rescue of frequency-dependent CMAP reduction in HSA-Lmna−/−; Rapsyn-Tg mice. Shown were ratios of the 10th over the first CMAP amplitudes. For 5 Hz, Lmna^f/f versus HSA-Lmna−/−, p = 0.1081; HSA-Lmna−/−; Rapsyn-Tg versus HSA-Lmna−/−, p = 0.9472. For 10 Hz, Lmna^f/f versus HSA-Lmna−/−, ***p = 0.0003; HSA-Lmna−/−; Rapsyn-Tg versus HSA-Lmna−/−, p = 0.0975. For 20 Hz, Lmna^f/f versus HSA-Lmna−/−, **p = 0.0013; HSA-Lmna−/−; Rapsyn-Tg versus HSA-Lmna−/−, *p = 0.0164. For 40 Hz, Lmna^f/f versus HSA-Lmna−/−, **p = 0.0026; HSA-Lmna−/−; Rapsyn-Tg versus HSA-Lmna−/−, *p = 0.0204. Data were shown as mean ± SEM, F_{(genotype)(2,6)} = 49.23, two-way ANOVA followed by Bonferroni's post hoc test, n = 3 mice per genotype. J, Reduced ratio of 2nd–10th CMAP amplitudes over the first CMAP amplitude at 40-Hz stimulations. 5th, Lmna^f/f versus HSA-Lmna−/−, *p = 0.0101; HSA-Lmna−/−; Rapsyn-Tg versus HSA-Lmna−/−, *p = 0.0316. 6th, Lmna^f/f versus HSA-Lmna−/−, **p = 0.0054; HSA-Lmna−/−; Rapsyn-Tg versus HSA-Lmna−/−, *p = 0.0307. 7th, Lmna^f/f versus HSA-Lmna−/−, **p = 0.0067; HSA-Lmna−/−; Rapsyn-Tg versus HSA-Lmna−/−, *p = 0.0268. 8th, Lmna^f/f versus HSA-Lmna−/−, **p = 0.0045; HSA-Lmna−/−; Rapsyn-Tg versus HSA-Lmna−/−, *p = 0.0310. 9th, Lmna^f/f versus HSA-Lmna−/−, **p = 0.0021; HSA-Lmna−/−; Rapsyn-Tg versus HSA-Lmna−/−, *p = 0.0166. 10th, Lmna^f/f versus HSA-Lmna−/−, **p = 0.0026; HSA-Lmna−/−; Rapsyn-Tg versus HSA-Lmna−/−, *p = 0.0204. Data shown as mean ± SEM, F_{(genotype)(2,6)} = 16.97, two-way ANOVA followed by Bonferroni's post hoc test, n = 3 mice per genotype. K–M, Increased mEPP frequencies and amplitudes in HSA-Lmna−/− mice by rapsyn expression. K, Representative mEPP traces. L, Increased mEPP frequencies in HSA-Lmna−/−; Rapsyn-Tg mice compared with HSA-Lmna−/− mice. Data were shown as mean ± SEM, F_(2,6) = 29.40, **p = 0.0022 for Lmna^f/f versus HSA-Lmna−/−; **p = 0.0078 for HSA-Lmna−/−; Rapsyn-Tg versus HSA-Lmna−/−; one-way ANOVA with Tukey's multiple comparison test, n = 3 mice per genotype. M, Increased mEPP amplitudes in HSA-Lmna−/−; Rapsyn-Tg mice compared with HSA-Lmna−/− mice. Data were shown as mean ± SEM, F_(2,6) = 30.27, **p = 0.0017 for Lmna^f/f versus HSA-Lmna−/−; *p = 0.0208 for HSA-Lmna−/−; Rapsyn-Tg versus HSA-Lmna−/−; one-way ANOVA with Tukey's multiple comparison test, n = 3 mice per genotype.