Although the severe effects of systemic TDP43 deficiency are a barrier to investigating loss-of-function, conditional deletion of Tardbp from motor neurons (using loxP flanked Tardbp mice crossed to Hb9-Cre recombinase expressing animals) resulted in delayed weight-gain, impaired rotarod performance, loss of spinal cord motor neurons and ALS-like pathology [52], [53]. The gene discussed is TARDBP; the disease is amyotrophic lateral sclerosis.