Antibiotic treatment that inhibits the development of colitis prevents growth failure in T/I mice.

<p>A. Mean body weight from weaning until 8 weeks of age is shown for female T/I mice that received food containing amoxicillin, clarithromycin, metronidazole, and omeprazole (antibiotics) or matched food lacking these drugs (placebo). The numbers of mice studied were: T/I, antibiotics (n = 6); and T/I, placebo (n = 11). SEMs averaged 0.5 across all days and groups; error bars are omitted for clarity. Although weights for both groups were statistically similar soon after weaning, the weights of the T/I mice that received placebo were significantly lower at 8 weeks of age than those for T/I mice that received antibiotics (p = 0.04; Student’s t-test). B. Colitis histologic scores are shown for these same mice. Each point represents a single mouse studied. A score of ≤12 indicates absence of colitis, while scores ≥ 25 indicate moderate to severe colitis. * indicates a significant difference from mice treated with placebo; p = 0.0003 (Mann-Whitney non-parametric test).</p

Systemic levels of leptin in T/I-het vs. T/I mice.

<p>Mean ± standard deviation of leptin levels did not differ between T/I-het (n = 7) and T/I (n = 11) mice when normalized to body weight (p = 0.08; Student’s t test).</p

Growth retardation and alopecia in a T/I pup, 24 days old, produced and nursed by a T/I dam.

<p>Hair is retained on the face and sparsely on the lower abdomen, with near total hair loss in other body regions.</p

Stool protein in WT, T-het/I, and T/I mice.

<p>Mean ± SEM of protein in the stool was similar in WT (n = 12), T/I-het (n = 10), and T/I mice (n = 21) at 9–11 weeks of age (ANOVA with Tukey’s post-test).</p

T cell metabolism is not altered in T/I mice with IBD.

<p>CD4⁺ T cells were isolated from spleen and mesenteric lymph nodes of T/I-het and T/I mice. Extracellular acidification rate (ECAR, panel A), basal oxygen consumption rate (OCR, panel B), and spare respiratory capacity (SRC, panel C) were measured using a Seahorse Extracellular Flux Analyzer.</p

Serum Chemokines in T/I-het vs. T/I Mice at 9 weeks of age^**.

<p>Serum Chemokines in T/I-het vs. T/I Mice at 9 weeks of age^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0152764#t002fn002" target="_blank">**</a>}.</p

Biochemical and physiologic parameters related to metabolic rate in T/I vs. T/I-het mice.

<p>8–9 wk T/I and T/I-het male mice were acclimated to single housing in a CLAMS metabolic chamber for 4 days, then measurements were recorded continuously over the next 72 hrs. Values shown are mean ± standard error of the mean for 8 mice per genotype. A. Oxygen consumption, VO₂; B. CO₂ production, VCO₂; C. Respiratory exchange ratio (RER); D. Heat production; E. Food consumption; F. Water consumption; G. Motor activity. Additional measurements made outside of the CLAMS unit included body temperatures (H) and blood glucose measurements (I). * indicates p< 0.05.</p

Effect of TNF and IL-10 deficiency on growth.

<p>A. Mean body weight is shown for female mice of the indicated genotypes from weaning until 28 weeks of age (n = 5 for T/I-het and T/I mice; n = 3–5 for WT, with 65 measurements per mouse). Although weights for all 3 genotypes were statistically similar at weaning, the weights of the T/I mice became significantly lower than their T/I-het littermates beginning at 8 wks and was lower than the WT mice beginning at 13 wks and they remained significantly lower for the remainder of the study (p < 0.05, 2 way ANOVA with Dunnett’s post-test). Similar trends were seen for male mice. SEMs averaged 0.8 g across all days and groups; error bars are omitted for clarity. B. Colitis histologic scores are shown for cohorts of 9–12 wk old mice. Each point represents a single mouse studied: WT (n = 11), <i>Tnf</i> ^-/- (n = 6), <i>Il10</i> ^-/- (n = 7), T-het/I (n = 17), T/I-het (n = 5), and T/I (n = 14). A score of ≤12 indicates absence of colitis, scores ≥ 25 indicate moderate to severe colitis, and the maximum possible score is 75. * indicates a significant difference from WT; p ≤ 0.0001 for both T-het/I and T/I (Kruskal-Wallis non-parametric test with correction for multiple comparisons).</p

Food Consumption by Mice with Varying Levels of TNF and IL-10 Deficiency.

<p>Food Consumption by Mice with Varying Levels of TNF and IL-10 Deficiency.</p

Reproductive success of dams with varying levels of TNF and IL-10 deficiency.

<p>Each point represents results of a single mating for the indicated dam genotypes. The mean number of pups/litter is indicated with a line. * indicates significant difference from WT (p < 0.0001; ANOVA with Dunnett’s post-test).</p