Fig. 1
Expression of TDP-43M337V affects motor phenotype. a Immunohistochemical staining for phosphorylated high molecular weight neurofilament (SMI-31) counterstained with Luxol fast blue shows no apparent loss of myelin in the corticospinal tracts. Inset = higher magnification of the corticospinal tract showing axonal cross sections (brown) and myelin (green). WM = white matter, GM = grey matter. b GFP is not expressed in the rat spinal cord when not fused to tau. c Human TDP-43 is not expressed in the TRE-TDP-43M337V rat spinal cord without the ChAT-tTA transgene. d Human TDP-43 is expressed in cholinergic motor neurons in the spinal cord of ChAT-tTA/TRE-TDP-43M337V rats (brown staining). All photomicrographs represent rats at 30 days post doxycycline (DOX) reduction. All images were taken at 20x, insets at 40x. e ChAT-tTA/TRE-TDP-43M337V rats exhibit a reduced number of motor neurons in lumbar spinal cord compared to non-expressing parental transgenic lines (n = 3/group, 30 days after DOX reduction, mean ± SEM). * = significant Dunn’s post-hoc test for multiple comparisons (p < 0.05) following a one-way ANOVA (p = 0.01). f Mixed ANOVA found a statistically significant interaction between the genotype (ChAT-tTA/TRE-TDP-43M337V) and DOX reduction time on hind paw initial contact time in CatWalk XT gait analysis (*p = 0.010; n ≥ 4/group), suggesting that TDP-43 expressing rats took longer to initially contact the walkway with 50% DOX reduction over time, compared to TDP-43 non-expressing controls. g There was a statistically significant interaction between the TDP-43M337V and DOX reduction time on hind paw stride length (n ≥ 6/group, p = 0.024). However, there was no significant main effect of time, suggesting that DOX withdrawn TDP-43 expressing animals generally took smaller strides over time, compared to TDP-43 non-expressing controls. h There was a statistically significant interaction between the TDP-43M337V and DOX reduction time on body speed (n ≥ 6/group, p = 0.039) but no main effect of time, suggesting that DOX reduced TDP-43 expressing rats generally slowed down over time, compared to controls