Figure 5.

Cells Expressing Mutant FUS Are Hypersensitive to dsRNA Toxicity

(A) Increased number of cleaved CC3-positive cells in poly(I:C)-stimulated ΔNLS_ho cultures. Cells were analyzed 24 h post-transfection. Data for two ΔNLS_het lines and two ΔNLS_ho lines were combined for the graph. 7 fields of view (×20 magnification) were included in the analysis per line. ^∗p < 0.05 (one-way ANOVA with Dunnett’s test). Representative images are also shown. Scale bar, 50 μm.

(B) Elevated levels of the proapoptotic factor CHOP in FUSΔNLS lines after poly(I:C) stimulation. Cells were analyzed by qRT-PCR 24 h post-transfection. Combined data for three ΔNLS_het lines and three ΔNLS_ho lines are shown (n = 3 for each line). ^∗p < 0.05 (Mann-Whitney U test).

(C) Mutant FUS P525L fibroblasts are more sensitive to poly(I:C) compared with control fibroblasts. Representative images and quantification of CC3-positive cells 8 h post-transfection are shown. 9 and 12 fields (×20 magnification) were included into analysis for control and P525L fibroblasts, respectively. Arrowheads indicate CC3-positive cells. ^∗∗∗∗p < 0.0001 (Student’s t test). Scale bars, 50 and 10 μm for bright-field images and fluorescent images, respectively.

In all panels, data are represented as mean ± SEM.