TARDBP and amyotrophic lateral sclerosis: ‘Hits’ can also be environmental factors, in order to tease out gene x environment interactions: for example, a recent study of low dose of the toxin β-N-methylamino-L-alanine, which is associated with Guam-ALS, given to mice expressing a TDP-43 transgene with a mild phenotype, showed a worsening of motor phenotypes in the treated versus untreated transgenic mice [92].