Tched controls [245,246]. On the contrary, overexpression of other TDP-43 ALS-linked mutations
Tched controls [245,246]. On the contrary, overexpression of other TDP-43 ALS-linked mutations led to progressive degeneration and several functional deficits in flies depending on the single mutation at situation, like aberrant eye 2-Bromo-6-nitrophenol web morphology (D169G, G298S, A315T, M337V, N345K), decreased life span and eclosion defect (G287S, A315T, G348C, A382T, N390D), climbing and crawling deficitsInt. J. Mol. Sci. 2021, 22,12 of(A315T), elevated larval turning time, reduced bouton numbers, improved or no modify of dendritic branching, increased active zone at NMJs (D169G, G298S, A315T, N345K), day and night sleep fragmentation (D169G, G298S, A315T, Q331K, N345K), cytoplasmic and axonal aggregates (D169G, G298S, A315T, N345K) [241,24750]. In other situations, mutant phenotypes cannot be clearly distinguished from these carrying WT TDP-43, since the latter shows similar traits for the mutant types; in fact, also the overexpression from the human WT TDP-43 might lead to aberrant eye morphology, eclosion defect, climbing and crawling defect, learning deficiency, vesicle transport dysfunction, elevated or no transform of dendritic branching at NMJs, and TBPH aggregates [233,235,237,239,247]. The above-mentioned controversial results among the distinctive mutant lines may possibly be resulting from variations on the genetic backgrounds and/or with the position in the UAS-TBPH insertion. Furthermore, overexpression of mutant TBPH (A315T, Q367X) was reported to induce aberrant eye morphology, axonal aggregates, crawling defect, eclosion defect, decreased bouton numbers, and decreased or no modify in dendritic branching at NMJs [236,247]. 7.3. Fmoc-Gly-Gly-OH site Drosophila Melanogaster Carrying FUS Mutations The cabeza (caz) will be the only ortholog gene of FUS in Drosophila melanogaster [251]. Caz LoF models, obtained by knockout technique, showed aberrant eye morphology, decreased viability, life span reduction, crawling and climbing defects, decreased synaptic branches and bouton quantity [237,25256]. GoF models, by GAL4/UAS-induced overexpression of WT or mutated human FUS have already been also investigated. The overexpression of human FUS mutants led to many phenotypic alterations, including aberrant eye morphology (R518K, R521C, R521G, R521H, R524S, P525L), eclosion defect (R518K, R521C, R521H, R521G), climbing and crawling defects (R518K, R521C, R521G, R521H, R524S, P525L), reduced synaptic bouton number (R521G, R524S, P525L) or no transform (R521C, R521H), and decreased active zone at NMJs (R518K, R521C, R521H, P525L) [237,25660], indicating that either the protein LoF or Gof induced a pathological phenotype. As within the case of TDP-43, the overexpression of WT human FUS induced a phenotype characterized by alterations that had been pretty much entirely superimposable to these observed together with the different FUS mutants [237,25659,261]. 7.4. Drosophila Melanogaster Carrying C9orf72 Mutations Drosophila melanogaster will not have a C9orf72 ortholog gene [262], thus generating it impossible to determine the consequence of C9orf72 LoF within this organism. As a result, fly models for C9orf72-associated ALS have already been developed by overexpressing G4C2 repeat RNA, modelling DPR protein toxicity, therefore revealing vital molecular insights [263]. Transgenic flies expressing 30 to 50 G4C2 repeat expansions, when in comparison to controls expressing three G4C2 repeats, displayed aberrant eye morphology, crawling and climbing defects, reduction of synaptic boutons and active zone at NMJs, and eclosion defect [127,26467]. Flies expressing dipeptide repeat pr.