WIPI4 loss of function induces ferroptosis in zebrafish. a, Zebrafish juveniles with wdr45 knockdown (wdr45 KD) by CRISPR injection had reduced lifespans compared with their uninjected siblings from the age of 4 weeks. Survival rate of WIPI4 CRISPR mutants and their uninjected siblings over a period of 7 weeks (n = 60 fish per group); log-rank Mantel–Cox test. b, Treatment of rho:EGFP transgenic fish with 10 μM Fer-1 from 5 to 10 d.p.f. rescued the loss of photoreceptors following wdr45 KD by CRISPR injection, whereas Fer-1 did not cause any change in the fluorescence rod area of uninjected fish. Representative images of sections across the eye of 10 d.p.f. rho:EGFP fish injected with wdr45-targeting CRISPRs and their uninjected siblings treated with DMSO or 10 μM Fer-1, respectively. Scale bar, 50 μm. c, Photoreceptor areas from the images in b; n ≥ 23 eyes per group. d, Increase in lipid peroxidation, represented by higher concentrations of MDA, in wild-type fish subjected to wdr45 KD by CRISPR injection at 5 d.p.f. compared with their uninjected siblings; n = 5 biologically independent experiments, 30 fish each. Data are the mean ± s.d. *P < 0.05 and **P < 0.01; two-tailed unpaired Student’s t-test. Source numerical data are provided. Source data
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