digestive/alimentary system
• mice exhibit defects in the intestinal epithelial cell barrier
• surface levels of E-cadherin are reduced in isolated colonic intestinal epithelial cells and organoid-derived monolayers
• colonic organoids show disorganized E-cadherin staining along the adherens junctions and increased puncta formation in the cytosol
• however, no differences are observed in the mRNA and protein levels or localization of other epithelial cell junction proteins (including occludin, ZO1, claudin 1 or claudin 2)
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• colon and small intestine epithelial tissues show significantly increased permeability to smaller solutes such as Lucifer Yellow (0.4KDa), but not to larger solutes such as FITC-dextran (4KDa)
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• mice exhibit impaired recovery from dextran sodium sulfate (DSS)-induced colitis as evidenced by an increased body weight loss, reduced colon length, and more severe colonic histopathology at day 13 after DSS treatment relative to wild-type controls
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immune system
• mice exhibit impaired recovery from dextran sodium sulfate (DSS)-induced colitis as evidenced by an increased body weight loss, reduced colon length, and more severe colonic histopathology at day 13 after DSS treatment relative to wild-type controls
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• following challenge with Citrobacter rodentium, mice exhibit a higher bacterial load in stool and increased translocation of C. rodentium to the mesenteric lymph nodes and spleen at day 5 as well as shortened colon length and more severe histopathology (including crypt damage) at day 12 post-infection relative to wild-type controls
• however, cytokine response is not impaired at 12 days post-infection
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homeostasis/metabolism
• intestinal epithelial cells isolated from the colon or small intestine show increased protein levels of cytohesin-1; epithelial monolayers derived from colonic organoids show increased levels of cytohesin-1 protein in both membrane and cytosolic protein fractions with no detectable changes in cytohesin-1 mRNA level
• organoid-derived intestinal epithelial monolayers show higher membrane-associated ARF6-GTP levels
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cellular
• organoid-derived colonic monolayers show a significantly increased migratory rate at baseline and during hepatocyte growth factor (HGF)-induced cell migration relative to wild-type controls
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