Platelet-specific deletion of SHARPIN ameliorates DSS-induced colitis. (A-G) SHARPIN^fl/fl GPIbα-Cre mice were provided autoclaved water or DSS, and then all mice were switched to water only, as indicated, and euthanized on day 9. (A-B) Mouse weight loss, represented as a percentage of original weight, for males (A) and females (B) (n = 8, n = 4, respectively) (**P < .01 by 2-way ANOVA analysis) (C) Colon length (n = 12/11, combined male and female mice). (Note: 1 SHARPIN^fl/fl GPIbα-Cre⁻ mouse died before the end of the experiment, leading to colon autolysis, yielding unequal n.) (D) Rectal bleeding in SHARPIN^fl/fl GPIbα-Cre⁺ (left) and SHARPIN^fl/fl GPIbα-Cre⁻ (right) mice, as indicated by the arrow. (E) Summary of rectal bleeding score (n = 9) (right). (F) Hematoxylin and eosin (H&E) staining of paraffin-embedded SHARPIN^fl/fl GPIbα-Cre tissue imaged at ×20 from the medial-distal region of the colon, showing extensive inflammation and ulceration in the SHARPIN^fl/fl GPIbα-Cre⁻ colons. (G) Histology score calculated from H&E-stained colon images (n = 4). *P < .05; **P < .01.