Fig. 1: Hepatic Mettl3 knockout in mice results in postnatal lethality.

a Genomic PCR characterization for tail and liver tissues (the top lane for liver tissues and the rest for tails) from 2 weeks old mouse of the indicated genotype. The top lane (floxdel) showed the exon 2–4 deleted alleles (amplified using F1 and R2 primer shown in (Supplementary Fig. 1c)) that could be detected only in Mettl3^flox/flox/Alb-Cre (Mettl3 cKO) mouse livers. The middle lane (Alb-Cre) showed the effective insertion of Albumin enhancer/promoter-driven Cre into the “genomic safe harbor” Hipp11 (H11) locus. The bottom lane displayed genotyping of heterozygous (Mettl3^flox/-) or homozygous (Mettl3^flox/flox) flox flanking alleles (amplified by F1 and R1 primer shown in (Supplementary Fig. 1c)) (3 experiments were repeated independently with similar results). b Quantitation of Mettl3 mRNA expression in livers of wild-type (WT) control (Control, also hereafter in similar experiments) and Mettl3 cKO mice at different time points postnatally via RT-qPCR (n = 3 for 1 day Control and 3 weeks cKO group; n = 5 for 3 weeks Control group; n = 4 for other groups). c Western blot for Mettl3 in Control and Mettl3 cKO mouse liver tissues at two weeks after birth (6 experiments were repeated independently with similar results). Gapdh was used as a loading control (also hereafter in similar experiments). d Immunohistochemistry staining of Mettl3 in 4 weeks old Control and Mettl3 cKO mouse livers (6 experiments were repeated independently with similar results). Scale bar = 50 μm. e The number of offspring with different genotypes from intercrossing Mettl3^flox/flox and Mettl3^flox/-/Alb-Cre mice. f Representative appearance of sex-matched Control mice and Mettl3 cKO littermates at 4 weeks after birth. g Body weight of male Control and Mettl3 cKO littermates at different time points after birth (n = 4 for 1 week cKO group; n = 6 for 4 weeks and 5 weeks Control groups; n = 9 for 3 weeks Control group; n = 12 for 3 weeks cKO group; n = 13 for 2 weeks Control group; n = 15 for day 1 and 1 week Control group; n = 7 for other groups). h Survival curves of Control, Mettl3 cKO, and Mettl3 heterozygous (Mettl3^flox/-/Alb-Cre) littermates (n = 25 for each group). Data in b and g were shown as mean ± SEM with the indicated significance (*P < 0.05, **P < 0.01, ***P < 0.001; two-tailed student’s t-test). Data in (h) were analyzed by Log-rank (Mantel-Cox) test with the indicated significance (***P < 0.001). Source data are provided as a Source Data file.