Knocking out C9ORF72 exacerbates axonal trafficking defects associated with hexanucleotide repeat expansion and reduces levels of heat shock proteins I

iPSCs with mutant C9ORF72 were edited using CRISPR/Cas9 (1) to knockout C9ORF72 or, alternatively, (2) to correct the ALS mutation, followed by differentiation into motor neurons. We tested the effects of mutations in C9ORF72 on iPSC-derived MNs by comparing to isogenic gene-corrected controls. In addition, we generated a knockout in MNs containing mutant C9ORF72 to test if this would exacerbate MN degeneration.