Table 3.
Differential spatial expression of CMT-causing mutations using specific GAL4-drivers results in similar CMT-like phenotypes in both YARS1CMT and GARS1CMT D. melanogaster models.
| Phenotype Observed | Transgene | CMT Associated Mutations | Spatial Expression (Driver Used) | References |
|---|---|---|---|---|
| Age-dependent locomotor deficits |
hYARS1 | G41R, del153-156VKQV, E196K | Ubiquitous (Actin-5c-GAL4) | [33] |
| Nervous system (elav-GAL4, nSyb-GAL4) | [33,37] | |||
| dGARS | G240R | Nervous system (nSyb-GAL4) | [43] | |
| hGARS1 | E71G, G240R, G526R | Glutamatergic neurons (OK371-GAL4) | [44,67,68] | |
| GFS morphological and electrophysiological deficits | hYARS1 | G41R, del153-156VKQV | Giant fiber (A307-GAL4) | [33] |
| dGARS | P234KY, G240R | [43] | ||
| hYARS1 | del153-156VKQV | Pre-synaptic expression in GF (C17-GAL4, R91H05-GAL4) |
[37] | |
| dGARS | P234KY | Pre-synaptically TTMn (C42.2-GAL4) or Post-synaptically TTMn (ShakB-GAL4) | [43] | |
| Neuromuscular junction defects * | dGARS | P234KY | Ubiquitous (1032-GAL4) | [64] |
| Mesoderm (how-GAL4) | ||||
| Muscle (MHC-GAL4) | ||||
| hYARS1 | E196K | Nervous system (nSyb-GAL4) | [37] | |
| hGARS1 | E71G, G240R, G526R | Glutamatergic neurons (OK371-GAL4) | [44,67,68] | |
| Muscle Denervation * |
hGARS1 | G240R | Motor neuron (D42-GAL4) | [44,68] |
| hGARS1 | E71G, G240R, G526R | Glutamatergic neurons (OK371-GAL4) | ||
| Muscle contractions defect * |
dGARS | P234KY, G240R | Ubiquitous (Tubulin-GAL4) | [64] |
| Muscle (MHC-GAL4) | ||||
| P234KY | Mesoderm (how-GAL4) | |||
| Nervous system (elav-GAL4) | ||||
| Reduction of dendritic coverage * |
hGARS1 | E71G, G240R, G526R | Class IV multidendritic sensory neurons (ppk-GAL4) | [44,68] |
| Rough eye | dGARS | P234KY | Eye photoreceptor cell (GMR-GAL4) | [43] |
| hYARS1 | E196K | [33] | ||
| Developmental lethality |
hYARS1 | G41R, del153-156VKQV, E196K | Ubiquitous (Actin5c-GAL4, Tubulin-GAL4) | [33] |
| hGARS1 | E71G, G240R, G526R | [44,68] | ||
| hYARS1 | E196K | Nervous system (nSyb-GAL4) | [37] | |
| hGARS1 | E71G, G240R, G526R | [44,68] | ||
| dGARS | P234KY | [33,43] | ||
| dGARS | P234KY | Nervous system (elav-GAL4) | [64] | |
| Mesoderm (how-GAL4) | ||||
| Muscle (MHC-GAL4) | ||||
| Short lifespan | hGARS1 | E71G, G240R, G526R | Ubiquitous (Tubulin-GAL4) | [44,67,68] |
| Inhibition of global protein translation * |
hGARS1 | E71G, G240R, G526R | Class IV multidendritic sensory neurons (ppk-GAL4) | [44,68] |
| Ubiquitous (Tubulin-GAL4) | ||||
| Glutamatergic neurons (OK371-GAL4) | ||||
| hYARS1 | G41R, del153-156VKQV, E196K | Class IV multidendritic sensory neurons (ppk-GAL4) | ||
| Glutamatergic neurons (OK371-GAL4) | ||||
| Transcriptional dysregulation | hYARS1 | E196K | Nervous system (nSyb-GAL4) | [37] |
| GARS1CMT
accumulation at the synapse * |
dGARS | P234KY | Ubiquitous (1032-GAL4) | [64] |
| Mesoderm (how-GAL4) | ||||
| Muscle (MHC-GAL4) |
* Phenotype observed at larval stage.