Figure 1. Schematic Representation of Different Drosophila Models of G₄C₂ Repeat Expansion.

Major features of the DNA constructs used for each model are presented. In all Drosophila G₄C₂ models, the UAS-GAL4 system is used to overexpress G₄C₂ repeats with different lengthes, and these models share common SV40 3′UTR containing a polyadenylation signal. In the (G₄C₂)₃₀-EGFP model, repeats are interrupted in the middle by a six base pair sequence and followed by the EGFP coding region containing the ATG initiation codon. The (G₄C₂)₃₆ construct contains uninterrupted repeats, while the (G₄C₂)₃₆-RO construct harbors stop codons between every 12 repeats. The intronic (G₄C₂)₁₆₀ construct mimics the human C9ORF72 locus, as 160 copies of repeat sequence are flanked by C9ORF72 intronic sequences and adjacent exons. In the (G₄C₂)₅₈-GFP model, 58 copies of repeats are upstream to the GFP codon region but without the ATG start codon. The (G₄C₂)₄₈ construct contains stop codons in each frame 5′ to the repeat sequence. The three columns on the right list DPR proteins detected in these models when phenotypes are observed; the proposed mechanism of toxicity; and the respective references.