Figure 5.

Mutant FUS MN Display Activated MAPK Signaling

(A) Chromatogram showing correction of homozygous FUS H517Q/H517Q iPSCs (designated H517Q) to heterozygous FUS+/H517Q (designated H517H). The yellow triangle indicates the position of the homozygous point mutation G/G (upper panel) and the corresponding heterozygous C/G genotype (lower panel) upon genome correction.

(B) Isogenic corrected iPSCs display a normal karyotype.

(C) Mutant and isogenic corrected iPSCs differentiate into ISL1+/TUJ1+ MNs as well as ISL1+/CHAT+ MNs with similar efficiencies.

(D) Western blot assay displaying activated p38 and ERK in mutant FUS MNs compared with the isogenic controls. JNK was not found to be activated in mutant FUS MNs. Lysates from two independent replicates were pooled and assayed in triplicate. Data indicate means ± SEM.

All scale bars indicate 50 μM.