digestive/alimentary system
• mice show exacerbated dextran sulfate sodium (DSS)-induced colitis, both acute and chronic, showing more severe colitis, greater body weight loss and delayed recovery, and shorter colons, increased inflammatory infiltrates with a more severe disruption of mucosal structures, increased cell death in colon and decreased intestinal epithelial cells (IEC) proliferation
• increased susceptibility to DSS-induced colitis is not due to microbiome shifts and bone marrow transplantation experiments indicate that nonhematopoietic cells are responsible for the severe colitis in mutants
• however, mice show normal enterocyte lineage allocation in the colon and normal architecture in resting conditions, normal number of goblet cells and mucus secretion, unaffected IEC proliferation and intestinal barrier permeability, no differences in microbial community alpha diversity and species composition
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• mice with DSS-induced colitis begin to die on day 7 after DSS treatment and all die by day 13 compared to 50% of wild-type mice
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immune system
• mice show exacerbated dextran sulfate sodium (DSS)-induced colitis, both acute and chronic, showing more severe colitis, greater body weight loss and delayed recovery, and shorter colons, increased inflammatory infiltrates with a more severe disruption of mucosal structures, increased cell death in colon and decreased intestinal epithelial cells (IEC) proliferation
• increased susceptibility to DSS-induced colitis is not due to microbiome shifts and bone marrow transplantation experiments indicate that nonhematopoietic cells are responsible for the severe colitis in mutants
• however, mice show normal enterocyte lineage allocation in the colon and normal architecture in resting conditions, normal number of goblet cells and mucus secretion, unaffected IEC proliferation and intestinal barrier permeability, no differences in microbial community alpha diversity and species composition
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• mice with DSS-induced colitis begin to die on day 7 after DSS treatment and all die by day 13 compared to 50% of wild-type mice
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mortality/aging
• mice with DSS-induced colitis begin to die on day 7 after DSS treatment and all die by day 13 compared to 50% of wild-type mice
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neoplasm
N |
• mice subjected to azoxymethane (AOM)/DSS (lower dose of DSS due to increased mortality) develop tumors to a similar extent as treated wild-type mice
• treatment of mice with AOM once a week for 6 consecutive weeks and aged for up to 24 weeks after last injection results in no differences in tumor formation from treated wild-type mice
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growth/size/body
N |
• normal body weight and colon length
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hematopoietic system
N |
• percentages and absolute numbers of myeloid cells, including macrophages, neutrophils, and dendritic cells in bone marrow, blood, and spleen are normal and development of CD4+ and CD8+ T cells and natural regulatory T cells in thymus, spleen, and mesenteric lymph nodes and activation status of CD4+ and CD8+ T cells are unaffected
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