Figure 2. Zip8 393T-KI male mice exhibit increased susceptibility to chemically induced colitis.

(A) Initial body weight of Zip8 393T-KI homozygous mice at 11.5–13 weeks of age was higher compared with that of WT and heterozygous mice. n = 16–20 male mice/genotype. (B) Zip8 393T-KI heterozygous and homozygous mice exhibited increased and more sustained weight loss in DSS-induced colitis model. Statistical analysis by linear regression (day 7–14). Slopes are equal between groups, but intercepts were significantly different between WT and Zip8 393T-KI heterozygous and homozygous mice (P < 0.0001), with no difference between Zip8 393T-KI heterozygous and homozygous mice (P = 0.9498). (C) Percentage of mice with rectal bleeding at day 5 and/or 6 was numerically higher in the heterozygous and homozygous mice (nonsignificant, χ² test). (D) Day 14 histology was consistent with more inflammation in Zip8 393T-KI homozygous mice, with crypt elongation, crypt branching (top right), and expansion of lamina propria immune infiltrate and squamous metaplasia (bottom right). Scale bar: 400 μm; 200 μm (right). Images are representative of n = 5–7 mice/genotype. (E) Zip8 393T-KI heterozygous and homozygous mice had increased Il6 mRNA, consistent with ongoing inflammation. Relative expression was graphed and normalized to Gapdh mRNA. n = 4–7 male mice/genotype. Statistical analysis by 1-way ANOVA with Kruskal-Wallis and Dunn’s multiple comparisons tests when 3 or more groups compared (A and E).