C9orf72 and amyotrophic lateral sclerosis: However, the elimination of mouse endogenous C9orf72 in various C9orf72 transgenic mice expressing HRE produced significant motor deficits [24,25], indicating a synergistic interaction between gain and loss of function mechanisms in ALS pathogenesis even if such interaction was not accompanied by the loss of ChAT positive spinal motor neuron or motor axons [25], suggesting a potential impact of the C9orf72 deficiency in skeletal muscle.