TARDBP and amyotrophic lateral sclerosis: In addition, expression of TDP-43 with ALS-causing mutations in transgenic mice was shown to induce TDP-43-dependent RNA splicing defects with age-related motor neuron degeneration, without detectable cytoplasmic TDP-43 aggregation (or nuclear TDP-43 depletion) [364], further suggesting that TDP-43-associated RNA splicing defects may suffice to drive neurodegeneration in animal models.