Fig. 3.
hUPF1 rescues cell death arising from TDP43 overexpression but not knockdown. (A) Expression of TDP43(WT) (n = 136) and TDP43(A315T) (n = 111) down-regulated en-TDP43 in 15–36% of transfected neurons, as judged by anti-TDP43 antibody reactivity. (B and C) Knockdown of en-TDP43 or en-UPF1 in mouse primary neurons using shRNAs. (Scale bar, 25 µm.) (D) en-TDP43 knockdown increased the risk of death in primary neurons, as determined by LFM, but survival was unaffected by hUPF1. Reduction of 40–50% in en-UPF1 (E) exacerbated neurodegeneration due to TDP43 overexpression (F). In C and E, *P < 0.05, ANOVA with Dunnett’s test. In D, n = 305–513 neurons per genotype. In F, n = 249–332 neurons per genotype. For both D and F, ns, P > 0.05; *P < 0.006, **P < 2 × 10−7, Cox hazards analysis. Results were pooled from 8 to 24 wells per condition, in duplicate.