Overexpression of sra exacerbates Aβ42-induced phenotypes in Aβ42-expressing flies. Overexpression of sra exacerbates Aβ42-induced phenotypes in Aβ42-expressing.

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Overexpression of sra exacerbates Aβ42-induced phenotypes in Aβ42-expressing flies. Overexpression of sra exacerbates Aβ42-induced phenotypes in Aβ42-expressing flies. (A-M) The eye phenotypes induced by ectopic expression of Aβ42 in the developing eye were aggravated by sra overexpression. The Aβ42-expressing adult eye (H) was severely distorted as a result of neurodegeneration when compared with the control eye (A,B,G). Overexpression of sra alone resulted in a marginally rough-eye phenotype (C,D) compared with that of the control (A,B,G). Overexpression of sra in Aβ42-expressing flies exacerbated the rough-eye phenotype (H-J). By contrast, sra deficiency (E) partially rescued the rough-eye phenotype (K) as compared with that of Aβ42-expressing flies (H). The rough-eye phenotype induced by sra overexpression was rescued by DIAP1 overexpression (F,L). Inset figures are high-magnification images. (M) The graph shows the relative eye size of each experimental group (Tukey–Kramer test, n≥9, *P<0.05, ***P<0.001). (N-P) Aβ42 levels do not change following expression of sra. (N,O) Aβ42 mRNA (N) and protein (O) in the larval eye discs of each group (N, Student's t-test, n=8; O, Student's t-test, n=7; NS, not significant). (P) Confocal images showing the presence of Aβ42 in larval eye discs of the indicated groups. More than 20 discs were observed for each group, and the representative images are shown. Magnification of the pictures, ×200. (Q) Representative images of Thioflavin-S staining in the brains of 20-day-old male flies. No prominent difference in staining was observed between brains of homozygous Aβ42-expressing flies with (elav>Aβ42+sraEY) or without (elav>Aβ42) sra overexpression. No signal was detected in the control (elav-GAL4). Magnification of the pictures, ×400. (R) Survival rates of pan-neuronal Aβ42-expressing flies with sra overexpression (elav>Aβ42+sraEY) during development. The effects of overexpressed sra (elav>sraEY) in the controls (elav-GAL4, UAS-Aβ42, sraEY) are also shown (Tukey–Kramer test, n≥250, *P<0.05, **P<0.01, ***P<0.001). (S) Effect of sra overexpression on the locomotor activity of pan-neuronal Aβ42-expressing flies. Climbing assay was performed using 10-day-old male flies (Tukey–Kramer test, n=100, ***P<0.001, NS, not significant). (T) Survival curve of pan-neuronal Aβ42-expressing male flies with sra overexpression (elav>Aβ42+sraEY). The lifespans of sra- (elav>sraEY) or Aβ42-(elav>Aβ42) expressing flies and control flies (elav-GAL4) are also presented (Kaplan–Meier estimator and log-rank test, n≥100). All data are expressed as mean±s.e.m. Soojin Lee et al. Dis. Model. Mech. 2016;9:295-306 © 2016. Published by The Company of Biologists Ltd