In the TDP-43 knock-in mouse model of ALS, many studies did not reveal prominent motor deficits in heterozygous mice (including Q331K, M337V and G298S).60-62 Huang et al. 63 reported that TDP-43WT/N390D mice, but not TDP-43WT/A315T mice, develop ALS pathologies at the molecular, cellular and behavioural (rotarod) levels, indicating mutation owing to differential effects in the mouse and human genetic backgrounds. The gene discussed is TARDBP; the disease is amyotrophic lateral sclerosis.