Skip to main content
Fig. 3 | Acta Neuropathologica Communications

Fig. 3

From: RNA dependent suppression of C9orf72 ALS/FTD associated neurodegeneration by Matrin-3

Fig. 3

MATR3 is a strong modifier of C9orf72 G4C2-hexanucleotide repeat expansion (HRE)-mediated neurodegeneration in vivo. a Representative images of Drosophila eyes showing G4C2 hexanucleotide repeat expansion mediated eye degeneration in transgenic flies expressing 3 repeats (3R), 30 repeats (30R), 36 repeats (36R) and 58 repeats (58R) in the Drosophila eyes driven by GMR-gal4 driver. Flies expressing G4C2-3R had a comparable eye phenotype to control (GMR-GAL4; EGFP). Flies expressing G4C2-30R, 36R and 58R repeats exhibited signs of external eye degeneration including ommatidial fusion, bristle disorganization, depigmentation, and necrotic patches (arrow). These flies were expressing the G4C2 repeat expansion in the background of UAS-EGFP (control transgene) to account for GAL4 dilution. b Transgenic expression of human MATR3 in the G4C2 flies significantly ameliorated the external eye degenerative phenotypes and restored ommatidial structure and pigmentation. c Quantification of eye phenotypes showed statistically significant rescue in eye degeneration in G4C2-HRE flies upon expression of MATR3 (Kruskal–Wallis test). n ≥ 50 flies per genotype. d Quantification of mRNA levels of G4C2-GFP in heads from flies expressing G4C2-30R and 58R that are GFP-tagged, revealed no change in G4C2-GFP mRNA levels upon MATR3 expression (Kruskal–Wallis test). n = 5 per genotype. e Kaplan–Meier survival curve of flies conditionally expressing G4C2-30R in adult neurons, driven by ElavGS-GAL4 driver, showed significant reduction in longevity (left) and in median survival (right) (Log-Rank Mantel Cox test). n = 100 flies per genotype. f Neuronal expression of G4C2-30R caused profound motor dysfunction in adults. Quantification of the percentage of flies that can climb in 30 s indicated severe locomotion defects in G4C2 30R-expressing flies. Expression of MATR3 partially rescued the motor defects (One-way ANOVA). n ≥ 30 flies per genotype. Error bars indicate S.E.M. *p value < 0.05; **p value < 0.01; ***p value < 0.001; ****p value < 0.0001

Back to article page
\