Fig 8.

Suppression of hTDP-43ΔNLS expression rescues motor phenotypes and restores lifespan in rNLS8 mice. a Hindlimb splaying phenotype of nTg control, rNLS8 mouse after 6 weeks of hTDP-43ΔNLS expression and rNLS8 mouse back on Dox after 6 weeks of hTDP-43ΔNLS expression (+Dox, 2 weeks back on Dox shown). b Weight loss reached a nadir at 6 weeks in rNLS8 mice back on Dox (n = 11 rNLS8 +Dox and n = 8 littermate nTg/monogenic controls). c MN number in lumbar SC, and d, e analysis of NMJ innervation in rNLS8 mice after 6 weeks of hTDP-43ΔNLS expression and at 3–4 months back on Dox (n = 3–4 per group), *p < 0.05 versus 6 weeks off Dox, image shows rNLS8 mouse at 6 weeks off Dox +12 weeks back on Dox. f Wirehang performance of rNLS8 mice back on Dox at 6 weeks, p < 0.001 from 3 weeks back on Dox versus 6 weeks off Dox, and g rotarod performance of rNLS8 mice back on Dox at 6 weeks, p < 0.05 at 1 week back on Dox and p < 0.001 from 2 weeks back on Dox versus 6 weeks off Dox, by repeated measures ANOVA with Bonferroni's post hoc test, n = 8. h Survival in rNLS8 mice back on Dox at 6 weeks (rNLS8 + Dox—blue line, n = 14, littermate nTg/monogenic controls—black line, n = 11) and in rNLS8 off Dox (rNLS—dotted red line, n = 19, also included in Fig. 4f). Triangles/circles indicate censored animals either killed for analysis or remaining alive