Fig. 6

Tdp-43∆NLS causes trapping of Xrcc4 and Ligase 4 in the cytosol of neurons. (A-B) Representative IF images of Tdp-43 and Xrcc4 colocalization in the cortex of sham and MN-Tdp-43∆NLS mice (A). (B) Analysis of the extent of colocalization of Tdp-43 and Xrcc4 IF signals using Mander’s colocalization coefficient. (C-E) Representative images of proximity ligation assay (PLA) between Tdp-43 and DNA Ligase 4 (Lig4) or Xrcc4 in the cortex of sham and MN-Tdp-43∆NLS mice. Cell bodies were counterstained with Alexa-Fluor 488-conjugated Nissl stain. PLA signals were visualized as red foci/puncta at 568 nm. Anti-Tdp-43 rabbit antibody was used against mouse normal IgG as negative control. Scale bar = 10 µm. (C). Quantitation of PLA signal intensity from 12 different microscopic fields per group for Tdp-43 vs Lig4 (D) and Tdp-43 vs Xrcc4 (E). Data are expressed as mean ± SEM and analyzed by multiple paired t-tests. *, P < 0.05; ****, P < 0.0001