Figure 3. SAB expression in male mice determines the susceptibility to APAP-induced liver injury in a JNK-dependent fashion. WT C57BL/6N male mice received Ad-lacZ or Ad-SAB. (A) Fourteen days later, SAB expression was analyzed by immunoblotting, and (B) APAP (150 mg/kg) was given i.p., and H&E staining was performed and serum ALT levels were determined after 24 hours. Original magnification, ×10. Scale bars: 100 μm. n = 3/group. ALT: *P < 0.05 versus Ad-lacZ-injected Sab iΔHep mice, by unpaired, 2-tailed Student's t test. Data are presented as the mean ± SD. (C) Sab fl/fl or Sab iΔHep mice received 0.05 5 × 10 9 to approximately 5 × 10 9 IU Ad-lacZ or Ad-SAB. Fourteen days later, SAB expression was determined by immunoblotting. Immunoblot is representative of 3 separate experiments. n = 3/group. *P < 0.05 versus Sab iΔHep + Ad-lacZ, by 1-way ANOVA with Bonferroni's correction. Data are presented as the mean ± SEM. (D) Mice received APAP (300 mg/kg, i.p.), and 24 hours later, liver sections were stained with H&E, and the necrotic area (percentage) was measured. Serum ALT (± SEM) (U/L) was measured. Scale bars: 100 μm. n = 3 mice/group. ALT: *P < 0.05, versus Ad-lacZ-injected Sab fl/fl mice; **P < 0.05, versus Ad-lacZ-injected Sab iΔHep mice, by unpaired, 2-tailed Student's t test. Data are presented as the mean ± SD. (E and F) Jnk1/2 fl/fl mice received AAV8-TBG-GFP (n = 3), AAV8-TBG-Cre (n = 5), or AAV8-TBG-Cre plus Ad-SAB (n = 3). Fourteen days later, JNK and SAB expression levels were determined by immunoblotting, or mice were treated with APAP to analyze liver injury and serum ALT levels. Scale bars: 100 μm. ALT: *P < 0.05, versus AAV8-TBG-GFP, by unpaired, 2-tailed Student's t test. Data are presented as the mean ± SD.
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