Fig. 1.

Overexpression of mutant TDP-43 leads to age- and dose-dependent neurodegeneration in the adult retina. (A–L) GMR Gal4 expression of TDP-43 D169G (D–F), G298S (G–I) and N345K (J–L) variants results in age-dependent loss of pigment compared with GMR Gal4 driver controls (A–C) at 25°C. Note that D169G depigmentation is milder than in G298S and N345K variants. (M–X) TDP-43 variants D169G TDP-43 (P–R), G298S TDP-43 (S–U) and N345K TDP-43(V–X) exhibit stronger surface phenotypes, including necrosis, compared with controls (M–O) when expressed at higher levels (29°C). Genotypes and ages are indicated. Anterior right, dorsal up. (Y) Western blot analyses showing TDP-43 expression in several transgenic lines. For each mutant variant we characterized multiple lines, two of which are shown. Genotypes are indicated on top; blotting antibodies are indicated on the left. Arrowheads on the right indicate full-length and C-terminus truncation of TDP-43. Tubulin was used as a loading control.