Figure 7.

Variants alter hTNPO2-induced phenotypes and penetrance in the fly wing and impact of the variants corresponds with their location within the protein

(A) Ectopic expression of UAS-hTNPO2:WT^HA using nub-GAL4 disrupts wing development, causing notching, blisters, and gain-of-vein phenotypes (arrows). p.Trp370Cys, p.Trp370Arg, and p.Ala546Val have less severe phenotypes whereas p.Gln28Arg and p.Asp156Asn are significantly more toxic. p.Trp727Cys has a moderately stronger gain-of-vein phenotype than hTNPO2:WT. Scale bar = 200 μm.

(B) Blister and notch phenotypes caused by hTNPO2 expression in the wing occurs in 50% of wings, representing penetrance. Penetrance is significantly different for all variants except p.Trp727Cys. Statistics: 1-way ANOVAs with Dunnett’s multiple comparisons test. No significance (n.s.) ≥ 0.05, ^∗p < 0.05, ^∗∗∗p < 0.001, ^∗∗∗∗p < 0.0001. Error bars denote SEM. Each dot represents the results from one cross with >50 animals scored. The mean from two independent experiments that included 2–3 individual crosses is shown.

(A and B) “UAS Control” is UAS-(empty).

(C) Table summarizing phenotype severity associated with variants when compared to hTNPO2:WT-associated phenotypes. Symbols: strong decrease in toxicity (green arrows), strong increase in toxicity (red arrows), mild increase in toxicity (orange arrows), no obvious difference in toxicity (dash). p.Trp727Cys strongly reduces toxicity in two situations and mildly increases toxicity in two situations, earning two green and one red arrow in the summary.