Fig. 2: Adult-onset, hepatocyte-specific deletion of NAE1 causes liver failure.
a Schematic diagram depicting intravenous injection of AAV8-TBG-Cre (AAV-Cre, Cre) to 12-week-old Nae1f/f mice to induce NAE1 deletion in mature hepatocytes. AAV8-TBG-eGFP served as a control (AAV-GFP, GFP). NAE1, GFP, and neddylated conjugates (N8-Conj.) were analyzed by Western blot in liver extracts of GFP and Cre mice at D10 and D14 post-virus injections. Arrowheads indicate neddylated CULs and CUL1. Representatives of three independent experiments were shown. b BW and liver weight normalized to BW of GFP and Cre mice at D21 (n = 6 per group) and D24 (n = 5 per group). c Plasma ALT and bilirubin levels of GFP and Cre mice at D21 and D24 post-virus injections (n = 5). Unpaired t-tests, two-tailed in b, c. P < 0.05, **P < 0.005. d Survival curves (GFP: n = 6; Cre: n = 5). Log-rank (Mantel-Cox) test. **P = 0.0008. e Representative images of H&E and Sirius red staining of liver sections, with pathological scores assessed for the portal (*P = 0.016), lobular (**P = 0.000085) inflammation, and fibrosis (*P = 0.016) (n = 4 per group). Scale bar: 250 µm. f Relative mRNA levels of inflammatory and fibrotic genes in livers as determined by qRT-PCR (n = 5 per group). *P < 0.05. g Liver hydroxyproline contents as normalized to tissue weights (GFP: n = 10; Cre: n = 8). *P = 0.0053. All experiments in e–g were performed in the livers of male GFP and Cre mice at D24 post-virus injections. Multiple unpaired t-tests with the Holm-Sidak method in (e, f). Unpaired t-tests, two-tailed in (g). GFP (black), Cre (red). All quantitative data were presented as mean ± SEM. Source data are provided as a Source Data file.
