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. 2014 Sep 22;211(10):1937–1945. doi: 10.1084/jem.20140214

Figure 2.

Figure 2.

Nuclear depletion of TDP-43 occurs in retinal neurons before neurodegeneration. (A) Post-mortem brain tissue from a human GRN mutation carrier was co-stained with the nuclear marker DAPI (blue) and an anti–TDP-43 antibody (green). Normal TDP-43 distribution is still observed in some neurons (arrowhead), but other neurons exhibit nuclear depletion of TDP43 (arrow) with or without apparent cytoplasmic inclusions. Bar, 10 µm. (B) Immunofluorescence confocal microscopy of TDP-43 in 18-mo-old retinal GCL neurons. Brightness of the TDP-43 channel was increased in insets to highlight loss of nuclear TDP-43 in Grn KO neurons. Bar, 1 µm. (C) Scatter plot of nuclear and cytoplasmic intensities of TDP-43 in GCL neurons of 18-mo-old Grn KO mice. n = 121–174 cells from 6 mice/genotype; ***, P < 0.001, mixed-effects multivariate linear regression mode; 2 independent experiments. Bars represent median values. (D) Significant reduction in the nuclear/cytoplasmic TDP-43 ratio was observed in 12-mo-old Grn-KO GCL neurons (**, P < 0.01) and 18-mo-old Grn-KO GCL neurons (**, P < 0.01). n = 217–357 cells from 5–7 mice/age/genotype, mixed-effects multivariable linear regression model; 2 independent experiments. Mean ± SEM is shown.