Fig. 2

A Zebrafish polg exons are shown as color-coded boxes corresponding to protein domains of the Polg peptide. Black arrows show the position of the CRISPR/Cas9-targeted site in exon 2 of the polg^ia302 mutant line, and the missense mutation in exon 22 of the polg^sa9574 mutant line. In the polg^+/+ (up) vs. polg^−/− (down) sequences, the CRISPR/Cas9-targeted site is in italic and the protospacer adjacent motif (PAM) is underlined. The new stop codons generated in both mutants are indicated with * = TGA, in red. B, Cpolg^ia302/ia302 individuals fail to survive to three weeks (B), while part of polg^sa9574/9574 animals can survive to adulthood (C). In the Kaplan–Meier survival curve for polg^sa9574, time is shown in days post-fertilization (dpf); N = 50 individuals per genotype. The Log Rank test was used for statistical analysis; polg^+/+ vs. polg^{sa9574/sa9574}: p < 0.0001. D Body length analysis in wt (polg^+/+), heterozygous (polg^+/ia302) and homozygous (polg^ia302/ia302) individuals. The body length of zebrafish polg^ia302/ia302 mutants is significantly reduced compared to controls at 15 dpf. Heterozygotes body length is indistinguishable from wt at all considered stages. N = 8, in triplicate; **p < 0.01. E Body length analysis in wt (polg^+/+), heterozygous (polg^+/sa9574) and homozygous (polg^{sa9574/sa9574}) individuals. The body length of zebrafish polg^{sa9574/sa9574} mutants is significantly reduced compared to control and heterozygous individuals at all considered stages. N = 8, in triplicate; *p < 0.05; **p < 0.01. F Representative images of a zebrafish polg^+/+ control and a polg^ia302/ia302 mutant at 16 dpf; a polg^+/+ control is compared with a polg^+/ia302 heterozygote at 90 dpf. G Representative images of a zebrafish polg^+/+ control and a polg^{sa9574/sa9574} mutant at 16 and 90 dpf.