Figure 2. Overexpression of mutant TDP-43 in neurons causes progressive paralysis in rats.
(A) The grip strength of forepaws (f) and hind paws (h) was measured for NEF-tTA/TRE–TDP-43M337V double-transgenic (M337V) and NEF-tTA single-transgenic rats. Data are means ± SD (n = 7). (B) Open-field assay revealed an unrecoverable reduction of mobility in M337V rats after TDP-43 transgene was turned on. Data are means ± SD (n = 7). (C) M337V rats rapidly developed paralysis after the transgene was turned on. Within 2 to 3 days, disease progressed from paralysis stage to end stages. (D–I) Cresyl violet staining revealed the structure of frontal cortex (D and E), hippocampus (F and G), and the ventral horn of the lumbar spinal cord (H and I). The tissues were taken from M337V rats at disease end stages (E, G, and I) or from NEF-tTA rats at matched ages (D, F, and H). (J and K) Stereological cell counting revealed the number of motor neurons (>25 μm in diameter) in lumbar cords (L3–L5) and revealed the number of neurons in dentate gyrus. Data are means ± SD (n = 5). *P < 0.05. All rats used were females and were constantly given Dox in drinking water (50 μg/ml) until they were 60 days old. Scale bars: 100 μm (D–E, H, and I); 200 μm (F and G).