Inhibition of TNF-α rescues erythroid defects in rps19-deficient zebrafish. (A) tnfα mRNA is upregulated in rps19 MO zebrafish compared to wild-type (wt) at 18 hpf. (B) Treatment of rps19 MO zebrafish with the TNF-α inhibitor etanercept rescued the erythropoietic (see arrows) and developmental defects. The average phenotype of each group is shown. (C) Expression of hbae1 is increased in rps19 MO zebrafish after etanercept treatment. (D) Etanercept treatment restores hemoglobin levels in zebrafish, as measured by Drabkin’s reagent at 54 hpf. (E) Morphologic defects in rps19-morphant zebrafish are alleviated with etanercept treatment. “Strong defects” are defined as kinks, curved body, absent/rudimentary eyes, and other severe growth abnormalities. “Mild defects” are defined as smaller or shorter embryos with both eyes present. “No defects” indicates absence of visible defects in zebrafish morphology. Embryos were scored 3 times, with the average shown in the figure. (F) rps19-morphant zebrafish treated with etanercept showed reduced expression of p53 targets p21 and il-6. (G) Treatment with etanercept restored Gata1 expression in rps19 MO zebrafish. (H) Levels of Gata1 also increased in rpl11-mutant (L11) zebrafish following etanercept treatment. Data are representative of 2 independent experiments. *P < .05; **P < .01; ***P < .001.