Fig. 1

rNLS8 mice recover motor function following hTDP-43ΔNLS suppression after disease onset. a Representative immunofluorescence images of rNLS8 lumbar MNs expressing high levels of cytoplasmic TDP-43 at 6 wks. off Dox compared to low levels of cytoplasmic TDP-43 after 8 wks. recovery following 6 wks. off Dox. Scale bar: 50 μm. The antibody used for immunostaining detects both human and murine TDP-43. b Comparison of immunofluorescence staining intensity for TDP-43 as shown in (a) in the nucleus and cytoplasm of lumbar MNs from rNLS8 mice at 6 wks. off Dox or 6 wks. off Dox followed by 6–8 recovery on Dox. The nuclear area was defined by reference to DAPI staining and the nuclear/cytosolic TDP-43 immunofluorescence intensity ratio was calculated for 40–50 cells per group. The latter metric was compared between groups by unpaired t test; ****p < 0.0001. c TreadScan gait analysis with stance graph for representative rNLS8 mice at 6 wks. off Dox compared to 6 wks. off Dox followed by after 8 wks. recovery on Dox. d Treadmill running speeds of rNLS8 mice after 6 wks. off Dox and after 6 wks. off Dox followed by 6–8 wks. recovery on Dox. N = 9 mice per group, t test; **p = 0.002. e Average traces of compound muscle action potential (CMAP) in the gastrocnemius (GC) muscle of rNLS8 mice after 6 wks. off Dox or 6 wks. off Dox followed by 6–8 wks. recovery on Dox. f Maximum CMAP amplitude in the GC muscle of rNLS8 mice after 6 wks. off Dox or 6 wks. off Dox followed by 10 wks. recovery on Dox (t test, ***p < 0.001). g The proportion of neuromuscular junctions in the fast hindlimb muscle tibialis anterior (TA) innervation in rNLS8 mice after 6 wks. off Dox or 6 wks off Dox followed by 6–8 wks. recovery on Dox (t test; ***p = 0.002)