Fig. 1

SETX loss-of-function exacerbates C9orf72 neurotoxicity pathways. a We transduced HEK293 cells with a lentivirus vector containing an interrupted synthetic construct encoding a GR30 dipepetide, and also treated with a scrambled control siRNA or SETX siRNA, as indicated. After 48 h, we measured cell death by performing a propidium iodide exclusion assay (n = 4 biological replicates). HEK293 cells transduced with lentivirus containing an empty vector served as the negative control. ANOVA with post-hoc Tukey test; *P < 0.05, **P < 0.01. b On DIV14, we transduced primary cortical neurons with a lentivirus vector containing an interrupted synthetic construct encoding a GR30 dipepetide, and with a lentivirus vector containing either a scrambled control shRNA or SETX shRNA, as indicated. After 24 h, we measured cell death by performing a propidium iodide exclusion assay (n = 4 biological replicates). Cortical neurons transduced with lentivirus containing the scrambled control siRNA served as the negative control. ANOVA with post-hoc Tukey test; *P < 0.05, **P < 0.01. c We cultured primary cortical neurons from C9^450C BAC transgenic mice, and on DIV14, we transduced these primary cortical neurons with a lentivirus vector containing either a scrambled control shRNA or SETX shRNA, as indicated. After 24 h, we measured cell death by performing a propidium iodide exclusion assay (n = 3 biological replicates). Cortical neurons from non-transgenic littermate control mice served as the negative control. ANOVA with post-hoc Tukey test; *P < 0.05, **P < 0.01. See Additional file 1: Table S1 for all P values. Error bars = s.e.m