Table 3.

Drosophila models of Amyotrophic Lateral Sclerosis.

Amyotrophic Lateral Sclerosis
Drosophila Model	Developmental Stage	Assay Used for Neuropathology	References
Drosophila Orthologs of Human Genes
FUS (Cabeza in Drosophila)
Ectopic expression of wildtype and disease–mutated FUS	Larva, Adult	Immunostaining to detect altered subcellular localization of Cabeza in larval motor neurons, adult eye morphology, lifespan	[96]
VCP
siRNA knockdown	Drosophila cell culture	Western blotting to detect accumulation of high molecular weight forms of ubiquitin	[97]
VAPB (Vap33 in Drosophila)
Ectopic expression of mutant and wild type VAP–33	Larva, Adult, Drosophila cell culture	Larvae: Larval wing imaginal disc, larval NMJ, adult brain, adult muscle, analysis of mitochondrial morphology in flight muscle; analysis of endoplasmic reticulum (ER) fragmentation in larval brains, Adult: analysis of eye morphology, analysis of cell death, ubiquitinated aggregates Drosophila cell culture: and ER stress in cultured Drosophila S2 cells	[98,99,100,101,102,103]
Overexpression of Human Transgenes
C9ORF72
Pan–neuronal expression of RNA–only constructs expressing (G4C2)106 repeats with both intronic (nucleus) and polyadenylated (cytoplasm) sense and antisense transcripts Pan–neuronal expression of UAS–RNA sense polyA constructs expressing 800–1000 and >1000 (G4C2) repeats	Adult	Lifespan, negative geotaxis, light microscopy for eye morphology	[104]
Eye and pan–neuronal expression of UAS–(G4C2)3 and UAS–( G4C2)30 constructs in eye and motor neurons	Adult	Lifespan, light, and SE microscopy for eye structure and ommatidia loss, locomotion assay	[105]
UAS–(G4C2)48 expression in Class IV epidermal sensory dendritic arborization neurons	Larva	Dendritic branching analysis using confocal microscopy	[106]
Eye and pan–neuronal expression of UAS constructs containing 3, 36 and 103 pure, and 36, 108 and ~288 RNA–only (G4C2) repeats	Embryo, Adult	Stereomicroscopy for eye structure, lifespan, egg–to–adult viability	[107]
Ectopic expression of UAS constructs containing 8, 28 and 58 (G4C2) repeats	Larva, Adult	Larval locomotion, larval salivary gland nuclear envelope morphology, adult eye morphology	[107,108,109,110]
Ectopic expression of UAS constructs containing 36 protein–coding and 160 RNA–only (G4C2) repeats	Larva, Adult	Dendritic branching, lifespan, eye morphology	[110]
Ectopic expression of UAS constructs containing 30 (G4C2) repeats	Cultured Drosophila S2 cells, larval salivary gland, adult eye	Nuclear import, adult eye morphology	[111]
TDP–43
Reduced and ectopic expression of wild type TDP–43	Larva, Adult	Larval and adult locomotion, larval NMJ morphology, adult mushroom body morphology, adult learning	[112]
Ectopic expression of wild type and disease–mutated variants	Larva, Adult, cultured motorneurons	Larval NMJ morphology, larval motorneuron death, larval glia, adult sleep	[113,114]
Ectopic expression of wild type and disease–mutated variants	Larval eye imaginal discs, Adult	Subcellular localization, lifespan, locomotor activity	[113]
Ectopic expression of wild type and mutant TDP–43 with and without a chaperone protein	Larva, Adult	Larval protein aggregation, adult eye morphology,	[115]
FUS
Ectopic expression of wildtype and disease–mutated FUS	Larva, Adult	Subcellular localization in larval motor neurons, adult eye morphology, lifespan	[96]
Ectopic expression of wildtype and disease–mutated FUS	Adult	Adult eye morphology,	[116,117,118]
Motor neuron expression of wildtype and disease–mutated FUS	Larva, Adult	Larval brain size, larval motorneuron subcellular localization, larval locomotion, adult eye morphology	[119]
UBQLN1/2
Ectopic expression of wild type and disease variants	Adult	Measurement of TDP–43 levels in adult eye lysates	[120]
Co–expression of human UBQLN and TDP–43	Larva, Adult	Larval NMJ morphology, lifespan, measurement of TDP–43 levels in adult head lysates, adult eye morphology, adult locomotion assays	[24,121]
VAPB
Expression of wild type human VAPB in Drosophila neurons	Larva	Larvae: Rescues lethality, NMJ morphology, and NMJ electrophysiology of loss–of–function mutations in Drosophila VAP–33	[122]
SOD–1
Ectopic expression of wild type and disease variants	Adult	Lifespan, locomotion, number of motorneurons, neuronal SOD–1 accumulation, glial stress response	[123]