J Clin Invest.
Ubiquitin accumulates in the motor neurons of ALS rats.
(A–F) Immunostaining revealed a marked accumulation of ubiquitin in the motor neurons of mutant TDP-43 transgenic rats. (G–I) Confocal microscopy revealed that ubiquitin aggregates accumulated in the motor neurons expressing mutant human TDP-43 (hTDP-43). ChAT–tTA-9/TRE–TDP-43M337V double-transgenic (M337V) rats were deprived of Dox at 60 days of age and were paralyzed at the age of 78 days. ChAT–tTA-9 single-transgenic (ChAT-tTA) rats were terminated at matched ages. Some M337V rats were treated with Dox (M337V + Dox) to prevent mutant TDP-43 from further expression after disease onset. Dox-treated rats were terminated at 90 days of age. Scale bars: 200 μm (A–C); 50 μm (D–F); 10 μm (G–I).