Fig. 2

TDP-43 acetylation-mimics generate hallmark disease pathology in vivo in mouse skeletal muscle. a Immunofluorescence analysis was performed on mouse tibialis anterior (TA) muscles electroporated with the indicated GFP-tagged TDP-43 plasmids for 4 days. b TA muscle sections were double-labeled with GFP (green) and dystrophin (Dys, red) antibodies to mark the muscle periphery, while nuclei were stained with DAPI (blue). c TA muscles expressing TDP-43-ΔNLS-K145Q were double-labeled with GFP and phospho-TDP-43 (P409/410) antibodies to mark pathological TDP-43 aggregates. White arrows highlight phosphorylated TDP-43 accumulation. d Electroporated TA muscles were harvested, fractionated into soluble and insoluble fractions, and analyzed by immunoblotting using TDP-43, P409/410, and GAPDH antibodies. Shown is a representative immunoblot from N = 3 independent experiments. e Quantification of d illustrates increased insoluble TDP-43 in muscles expressing TDP-43-ΔNLS-K145Q. Error bars indicate SEM, and the asterisk indicates statistical significance with ***p-value < 0.001 and **p-value < 0.01, as measured by Student’s t-test. Scale bar = 50 μm