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