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. 2015 Oct 16;24(25):7241–7254. doi: 10.1093/hmg/ddv424

Figure 1.

Figure 1.

208 TDP-43 CTF is insoluble and located in the cell bodies and dendrites of neurons in 208 TDP-43 Tg mice. (A) IB analysis of RIPA (R)- and urea (U)-soluble protein fractions of various brain regions from littermate control and 208 TDP-43 Tg mice at 6 months off Dox, using C-terminal TDP-43 PAb. Solubility and levels of endogenous full-length TDP-43 are unaltered in 208 TDP-43 Tg mouse, and 208 TDP-43 CTF is expressed in the cortex, hippocampus and olfactory (olf) bulb and is predominantly R-insoluble. Higher intensity images (dark) show the presence of at least four distinct 208 TDP-43 CTF protein bands, and low levels of 208 TDP-43 CTF in the brain stem and cerebellum. GAPDH is shown as a loading control and approximate-molecular-weight markers in kilodaltons are shown in the right. (B) IHC for hTDP-43 in 208 TDP-43 Tg mouse reveals widespread cytoplasmic punctate neuronal 208 TDP-43 CTF in (C) cortex and hippocampus, including the (D) CA1 and (E) DG regions, as well as in (F) olf bulb and (G) striatum at 6 months off Dox. (H) Rare Purkinje cells in the cerebellum are also positive for hTDP-43 with (I) no expression in the spinal cord. Images are representative of n ≥ 3 mice at each of 2 weeks, 6, 10, 16, 19 and 24 months off Dox. (J–O) IF for hTDP-43 shows co-localization of 208 TDP-43 CTF with dendritic marker MAP2 but not axonal marker pNF in 208 TDP-43 Tg mouse at 16 months off Dox. Nuclei (DAPI) are shown in blue in the merged images. Scale bars: B, 500 μm; C–E, 50 μm; F–I, 50 μm; J–O, 20 μm.