TARDBP and amyotrophic lateral sclerosis: Further substantiating the presence of both loss and gain of function mechanisms are findings that expressing human TDP-43 without a nuclear localization signal (ΔNLS) in mice causes, among other ALS phenotypes, a nuclear loss of endogenous mouse TDP-43, and doxycycline induced removal of ΔNLS TDP-43 restores neuromuscular phenotypes to normal, respectively (Walker et al., 2015).