LPS induces severe liver failure in Sharpin-deficient mice.

<p>Wt and Sharpin-deficient mice (age: 9 weeks) were injected with LPS (4 mg/kg i.p.; 7 animals per genotype; 4 animals per genotype in saline injected control group). A. Survival curve. Three out of seven Sharpin-deficient mice died within the first 8 hours after injection. B. Serum ALT activity. Surviving animals were sacrificed after 8 hours and analyzed for serum alanine aminotransferase (ALT) levels. C. TNFα release. Serum TNFα levels were determined 1 hour after LPS treatment from all mice (including those which died within the first 8 hours) by ELISA. D–H. Pathological examination after 8 hours of treatment. Liver sections were H&E stained. Note the presence of lymphocytic infiltrates in liver from Sharpin-deficient mice (E,G) as well as necrosis after LPS injection (G,H). I. Activation of the caspase cascade. Liver tissue lysates of saline (S) and LPS (L) treated mice were analyzed by Western blotting using Caspase-3 and Caspase-8 specific antibodies, as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0029993#pone-0029993-g003" target="_blank">Figure 3</a>. Note the appearance of cleaved caspases in LPS treated Sharpin-deficient mice only (unspecific band marked with an asterisk).