SOD1 and amyotrophic lateral sclerosis: Interestingly, the generation of single-copy/knock-in mutant SOD1 models (A4V, H71Y, L84V, G93A and G85R) allowed for the dissection of the specific impact of different mutations on cholinergic versus glutamatergic motor neuron degeneration, showing that ALS pathogenesis is neuronal subtype-specific and characterized by both gain-of-toxic-function and loss-of-function [111].