Hepatocyte-specific NEMO-deleted mice (NEMO^Δhepa) are protected against Fas-mediated apoptosis. (A) Survival curve after i.p. injection of 0.5 µg/g Jo2, evidencing the resistance of NEMO^Δhepa mice to Fas-mediated death. (B–D) Macroscopic view of livers 3 h after Jo2 (B), liver weight/body weight ratio (B), serum transaminases (C), and H&E staining (D) showed fulminant hepatitis in NEMO^f/f mice after Jo2, whereas NEMO^Δhepa remained unaffected. (E and F) TUNEL (E) and caspase 8 and 3 (F) activity analysis confirmed Jo2 apoptosis. Activity is represented in times versus untreated NEMO^f/f. (G and H) Fas mRNA and IHC analysis in whole liver (G) and isolated primary hepatocytes (H) showed stronger expression in WT compared than in NEMO^Δhepa mice. (I) TNF mRNA and cellular location indicated by IHC. (J) Western blotting showed phosphorylation of JNK1 (p45) and JNK2 (p54) in NEMO^f/f mice after Jo2. JNK1 and GAPDH act as loading controls. Bars, 50 µm. Data are representative of three independent experiments. n = 4. *, P < 0.05; **, P < 0.01; ***, P < 0.001 (NEMO^f/f vs. NEMO^Δhepa). §§, P < 0.01; §§§, P < 0.001 (NEMO^f/f vs. Jo2/NEMO^f/f). Error bars represent SD.