Fig. 4
Neuronal TDP-43 proteinopathy is localized to the ventral thalamus of aged GrnR493X/R493X mice. Representative western blots of hemibrain RIPA-soluble and -insoluble lysates from 18 month old Grn+/+ and GrnR493X/R493X mice probed for TDP-43 expression. a Expression of full-length TDP-43 in Grn+/+ and GrnR493X/R493X hemibrains in soluble and insoluble lysates was analyzed by western blotting, using RIPA-soluble actin as the loading control (no actin detected in insoluble urea fraction). Arrows indicate TDP-43 CTFs, and the * demarks a remnant TDP-43 signal observed upon reprobing stripped RIPA-soluble TDP-43 blot with actin antibody. Densitometric quantification of brain-wide full-length TDP-43 expression in soluble (b) and insoluble (c) lysate fractions were normalized to RIPA-soluble actin and Grn+/+ levels. d Representative hippocampal/thalamic tilescans highlighting the neuronal (TUJ1, green) TDP-43 (red) proteinopathy phenotype in the ventral thalamus of 18 month old GrnR493X/R493X mice (scale bar, 500 µm). e High magnification images from the thalamic VPM/VPL regions demonstrating neuronal cytoplasmic accumulation of TDP-43 in 18 month old GrnR493X/R493X mice (DAPI, blue; scale bar, 10 µm). For western analysis n = 6 mice were used per sex/genotype; values are shown as mean ± SEM; ns = not significant, **p < 0.01, Student’s t-test