Table 3.
Disease modifiers identified in Drosophila FUS-ALS models
| Disease modifier | Fly transgenic construct | Phenotypic rescue | Refs. |
|---|---|---|---|
|
altFUS suppression |
Elav-GS > UAS-altFUSØ | Motor behavior | [119] |
|
ter-94 overexpression |
GMR-Gal4 > UAS-Caz-IR363-399;UAS-ter94 | Motor behavior, lifespan | [134] |
|
Phospholipase D pathway modulation |
GMR-Gal4 > UAS-FUSR521C | Eye morphology | [91] |
|
Drosophila muscleblind downregulation |
GMR-Gal4 > FUS;mblRNAi D42-Gal4 > FUS;mblRNAi |
Eye morphology, motor behavior, NMJ | [136] |
|
Drosophila Rm62 overexpression |
GMR-Gal4 > UAS-FUS; Rm62OE GMR-Gal4 > UAS-FUSR521C; Rm62OE GMR-Gal4 > UAS-FUSR518K; Rm62OE |
Eye morphology | [143] |
|
ElavGS-Gal4 > UAS-FUS; Rm62OE ElavGS-Gal4 > UAS-FUSR521C; Rm62OE ElavGS-Gal4 > UAS-FUSR518K; Rm62OE |
Motor behavior | ||
|
Nucleoporin 154 downregulation |
CCAP-Gal4 > UAS-FUS;Nup154RNAi | FUS-induced neurotoxicity | [129] |
|
Exportin 1 downregulation |
CCAP-Gal4 > UAS-FUS;Xpo1RNAi | FUS-induced neurotoxicity | |
|
Nucleoporin 62 downregulation |
D42-Gal4 > UAS-FUSR521C; Nup62RNAi D42-Gal4 > UAS-FUSR518K; Nup62RNAi ElavGS-Gal4 > UAS-FUSP525L; Nup62RNAi |
Nuclear abnormalities, lifespan | [145] |
|
Hippo downregulation |
GMR-Gal4 > UAS-Caz-IR;hpoKS240 Elav-Gal4 > UAS-Caz-IR;hpoKS240 |
Eye morphology, motor behavior | [147] |
|
Hippo downregulation |
GMR-Gal4 > UAS-FUS;hpo GMR-Gal4 > UAS-FUS;jun |
Eye morphology | [148] |
|
Parkin overexpression |
GMR-Gal4 > UAS-FUS;UAS-parkin Elav-Gal4 > UAS-FUS;UAS-parkin |
Eye morphology, motor behavior | [149] |