Pathogenic VCP/TER94 Alleles Are Dominant Actives and Contribute to Neurodegeneration by Altering Cellular ATP Level in a Drosophila IBMPFD Model
Figure 9
Neurodegeneration induced by pathogenic TER94 mutants can be suppressed under dark conditions.
(A–Hi) Confocal images of adult retinas expressing indicated transgenes under the control of Rh1-GAL4 stained with phalloidin (red), anti-VCP (green), and anti-Lamin (blue) antibodies. Freshly eclosed flies were raised under L/D (A–H), or D/D condition (Ai–Hi). Arrowheads in E and Ei indicate large TER94-containing structures in degenerated (E) and recovered (Ei) retinas. Scale bar: 10 µm. (I) Quantification of rhabdomere numbers per unit eye under L/D and D/D conditions. 210 to 388 unit eyes from ≥ six eyes are scored in each group. Values shown represent mean ± SE. * p<0.05; ***p<0.001 compares L/D to D/D conditions in each genotypes (one-way ANOVA with Bonferroni's multiple comparison test). Genotypes: (A and Ai) UAS-LacZ/+; Rh1-GAL4,UAS-LacZ/+, (B and Bi) UAS-TER94wt/w; Rh1-GAL4,UAS-LacZ/+, (C and Ci) Rh1-GAL4,UAS-LacZ/UAS-TER94R152H, (D and Di) Rh1-GAL4,UAS-LacZ/UAS-TER94R188Q, (E and Ei) UAS-TER94A229E/+; Rh1-GAL4,UAS-LacZ/+, (F and Fi) UAS-TER94K2A/+; Rh1-GAL4,UAS-LacZ/+, (G and Gi) UAS-Q108/+; Rh1-GAL4,UAS-LacZ/+, (H and Hi) UAS-MJDtr-Q78/+; Rh1-GAL4,UAS-LacZ/+.