Fig. 1: Embryonic-onset, hepatocyte-specific deletion of NAE1 causes liver failure and premature death.
a Schematic diagram depicting the generation of Nae1f/f; Alb-Cre + (LKO) mice with embryonic-onset hepatocyte-specific deletion of NAE1 by crossing Alb-Cre + mice with Nae1 floxed (Nae1f/f) mice. Nae1f/f mice served as wild-type (WT) controls. Western blot of NAE1 and neddylated conjugates (N8-Conj.) in liver extracts of WT and LKO mice at P7, P10, and P14 Arrowhead indicates neddylated CULs and CUL2. Two independent experiments. b BW of WT and LKO mice till postnatal 30 days (n = 6 per group). **P < 0.005. c Survival curves of WT and LKO mice (n = 6 per group). Log-rank (Mantel-Cox) test. *P = 0.0183. d Liver weight as normalized to BW at P10 (WT: n = 9; LKO: n = 9, **P = 0.000043) and P14 (WT: n = 8; LKO: n = 8, **P = 0.000275). e Gross morphology of livers at P14 and P21. Scale bar: 25 mm. f Plasma ALT (WT: n = 10; LKO: n = 9, **P = 0.0002) and bilirubin (WT: n = 5; LKO: n = 6, **P = 0.0006) levels of WT and LKO mice at P14. g H&E and Sirius red staining of liver sections, pathological scores for portal (n = 4 per group, *P = 0.024) and lobular (n = 4 per group, **P < 0.0001) inflammation as well as fibrosis based on Sirius red staining (n = 6 per group, **P < 0.0001) at P14. Yellow circle: the necrotic area; Yellow arrowhead: acidophilic body; Black circle: ductular proliferation; Blue circle: infiltrating neutrophils. Scale bar: 100–250 µm. h–i Relative mRNA levels of inflammatory and fibrotic genes in livers of P14 WT and LKO mice as determined by qRT-PCR (n = 6 per group). *P < 0.05, **P < 0.005. j Liver hydroxyproline contents as normalized to tissue weights in P14 WT and LKO mice (n = 9 per group). *P = 0.024. Male mice were used. Multiple unpaired t-tests with the Holm-Sidak method in (b, d, h, i). Unpaired t-test, two-tailed in (f, g, and j). WT (black), LKO (blue). All quantitative data were presented as mean ± SEM. Source data are provided as a Source Data file.
