Fig. 1

A mouse model (TDP-43 cKO) with αCaMKII promoter-directed depletion of TDP-43 in forebrain neurons. a Immunofluorescence staining analysis of brain sections from a cohort of 2-month-old Ctrl and TDP-43 cKO mice (TDP-43, magenta; NeuN, green; DAPI, blue). Cortex, CTX; cornu ammonis area, CA; dentate gyrus, DG. Scale bar represents 100 μm. b Western blotting analysis of the relative expression levels of TDP-43 and GFAP proteins in different tissues including cortex, hippocampus, cerebellum, and spinal cord of 3- and 12-month-old TDP-43 cKO mice and Ctrls. Note that ~ 50% reduction of TDP-43 protein level in the hippocampus and ~ 60% reduction of TDP-43 protein level in the cortex, but not in the cerebellum, and spinal cord in TDP-43 cKO mice. The Western blot patterns are exemplified in b, and the results of statistical analysis by unpaired student’s t test are shown in c P < 0.05 was considered significant. Data are represented as the average of 4 mice per group, with error bars reported as SEM. d Kaplan-Meyer survival curves of TDP-43 cKO mice and the Ctrls. Note the significantly shortened lifespan of TDP-43 cKO mice (P < 0.0001, log-rank Mantel-Cox test). The mean survival days are 28.8 months for the Ctrl mice and 17.2 months for the TDP-43 cKO mice