Ubiquitous expression of APP, BACE, and DPsn as a model system to identify genetic modifiers and validate pharmacologically active agents
| Actin-GAL4> | Ratio of flies expected | Ratio of flies scored | Wing phenotype |
|---|---|---|---|
| (1) UAS-DPsn/+ | 1:4 (0.25) | 1:4 (0.25) | Wild type |
| (2) UAS-BACE/UAS-DPsn | 1:4 (0.25) | 1:4 (0.25) | Wild type |
| (3) UAS-APP;UAS-BACE/+ | 1:4 (0.25) | 1:40 (0.025) | Ectopic veins (75%) |
| (4) UAS-APP;UAS-BACE/UAS-DPsn | 1:4 (0.25) | 1:97 (0.01) | Ectopic veins (100%) |
| (5) UAS-APP;UAS-BACE, psnC4/+ | 1:4 (0.25) | 1:13 (0.077) | Weak ectopic veins (70%) |
| (6) UAS-APP | 1:4 (0.25) | 1:127 (0.008) | Wild type |
| (7) UAS-APPL1;UAS-DPsn/+ | 1:4 (0.25) | 1:4 (0.25) | Wild type |
| Nonsupplemented | Vehicle supplemented | Inhibitor supplemented | Wing phenotype | Treatment | |
|---|---|---|---|---|---|
| (8) UAS-APP;UAS-BACE523/UAS-DPsn | 1:17 (0.06) | 1:18 (0.06) | 1:6 (0.17) | Weak ectopic veins (100%) | 10 nM BACE inhibitor |
| (9) UAS-APP;UAS-BACE406/UAS-DPsn | 1:100 (0.01) | 1:97 (0.01) | 1:22 (0.045) | Ectopic veins (100%) | 100 nM γ-secretase inhibitor |
| (10) UAS-DPsn/+ | 1:2.6 (0.38) | 1:3 (0.33) | 1:2.7 (0.37) | No ectopic veins | 10 nM BACE or 100 nM γ-secretase inhibitor |
Ratios of flies expressing the indicated transgenes under the control of the actin-GAL4 driver to nonexpressing flies. A comparison of expected and scored ratios indicates increased lethality during development of the fly. Lethality rate and wing phenotypes of transgenic flies (lines 1-7) and of transgenic larvae raised on nonsupplemented and vehicle supplemented versus BACE- or γ-secretase inhibitor supplemented medium (lines 8-10) are shown.