TARDBP and amyotrophic lateral sclerosis: In summary, rNLS8 Tg mice exhibit ALS/FTLD-TDP features including both toxic gain-of-function and TDP-43 loss-of-function phenotypes, including the accumulation of phosphorylated TDP-43 containing lesions (the most consistent neuropathology of ALS/FTLD-TDP) [10, 27] and loss-of-function changes in RNA regulation related to nuclear depletion of TDP-43.