An Enhanced Immune Response of Mclk1+/− Mutant Mice Is Associated with Partial Protection from Fibrosis, Cancer and the Development of Biomarkers of Aging
Figure 1
Favorable outcomes after infection of Mclk1+/− mutants with Salmonella Typhimurium.
A. Liver bacterial loads were evaluated 40 days after infection in 3 months-old mice and were lower in Mclk1+/− mutants. Three independent experiments were carried out. In each experiment, the average CFU per gram of tissue of each mutant (Mclk1+/−) and wild type animal (Mclk1+/+) was normalized to the average of the wild type group in that experiment. In total 35 wild type animals and 23 mutants were normalized in this way and the results pooled. The mean ± S.E.M. of the pool is shown. * indicates p<0.05. B. Liver fibrosis was determined in infected and uninfected groups on day 40 after infection using Picrosirius Red staining. The fraction of the area of sections that stain for collagen is shown. The mean ± S.E.M. are shown. There were 9–14 animals in each group. C. and D. Oxidative damage to proteins was evaluated by the Oxyblot assay. All samples used were from littermate pairs. A representative result is shown in C. The intensity of staining in each lane was quantified and normalized by that of the wild type in the same blot. The mean ± S.E.M. of each group is shown on the graph and paired t-tests were used for comparisons. E. Oxidative damage to DNA was determined by measuring 8-OHdG levels using purified total liver DNA. Littermate pairs were used (Mclk1+/− vs. Mclk1+/+): 5 pairs without infection and 6 pairs sacrificed 40 days after infection. The mean ± S.E.M. of each group is shown in the graph; paired t-test were used for comparisons. F. Plasma ALT activity was measured 40 days after infection. There were 8–14 animals in each group and the mean ± S.E.M. of each group are shown. For B−F, the differences between the mutant and wild type groups are significant with, but not without, infection at p<0.05. All experiments in this figure were carried out with males.