In contrast, studies in C9orf72 null mouse models detected only mild cognitive and behavioral deficits related to the ALS–FTD phenotype; however, loss of C9orf72 in combination with expression of G4C2 repeat RNAs resulted in an exacerbated disease phenotype in mice and in induced pluripotent stem cell (iPSC) derived neurons from patients [7,10–14]. This evidence concerns the gene C9orf72 and amyotrophic lateral sclerosis.