Mice with a Knockin Mutation in the UBA Are Acutely Sensitive to TNF-Induced Systemic Inflammatory Response Syndrome
(A and B) Body temperature and survival of WT (A, n = 11; B, n = 12) and corresponding littermate cIAP1UBAmut (A, n = 8) or cIAP2−/− (B, n = 11) mice injected with 4 μg/20 g body weight of mTNF. Data are representative of two independent experiments. Error bars represent SD. Survival curves were compared using log-rank Mantel-Cox test (∗p < 0.05, ∗∗∗p < 0.001).
(C and D) Plasma samples of WT and cIAP1UBAmut (C) or cIAP2−/− (D) mice were collected at the indicated time points following challenge with mTNF (4 μg/20 g body weight, intravenously [i.v.]) and analyzed for activities of LDH, AST, and ALT. n = 4 per time point and genotype. Data are presented as mean ± SD, ∗∗p < 0.01; statistics were performed using two-way ANOVA.
(E and F) TUNEL staining (E) and quantification (F) of liver sections of WT and cIAP1UBAmut mice used in (C) and (D).
Data in (A) and (B) were obtained from two sets of animals, while the data shown in (C)–(F) were obtained from a third set of animals. Graphs show mean ± SD, ∗∗p < 0.01; statistics were performed using two-way ANOVA.