Fig. 5

Normal human SETX can rescue motor impairment caused by neuronal expression of GR(1000) in transgenic flies. We directed pan-neuronal expression of GR(1000)-GFP or GFP only, in combination with either normal FLAG-SETX(wt) or FLAG-SETX(L389S) or FLAG only, by crossing transgenic flies with flies expressing the nSYB-GAL4 driver. At 14 days of age, we collected 30–50 male flies, and performed a negative geotaxis climbing assay to assess motor function by measuring the distance traveled upward (mm) in 20 s. Flies expressing the GR(1000)-GFP transgene in combination with a separate FLAG transgene displayed a reduced mean climbing distance of 32.8 mm, which was a dramatic decrease from the 114.4 mm observed in flies expressing the GFP transgene and FLAG transgene (ANOVA with post-hoc Tukey test; ****P < 0.0001). Neuronal co-expression of GR(1000)-GFP with FLAG-SETX(wt) yielded an increase in mean climbing distance to 80.4 mm, which represented a significant rescue (ANOVA with post-hoc Tukey test; ****P < 0.0001); however, neuronal co-expression of GR(1000)-GFP with FLAG-SETX(L389S) resulted in a mean climbing distance similar to the motor performance observed in flies expressing the GR(1000)-GFP transgene in combination the FLAG-only transgene (ANOVA with post-hoc Tukey test; P = n.s.). See Additional file 1: Table S1 for all P values. Error bars = s.e.m