Analysis Tools
digestive/alimentary system
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• unchallenged mice show a significant shift in the Bacteriodetes:Firmicutes phyla ratio in the small intestine with an average ratio of 66:29 relative to 82:15 in wild-type controls
• however, no alteration in gut permeability is observed at baseline and the amount of secreted fecal IgA is normal
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• in culture, 24 hours after 1 Gy treatment, enteroids show significantly higher expression of Cdkn1a (aka p21 or p21WAF1/CIP1) than wild-type enteroids
• however, expression of Cdkn2c (aka p18Ink4c, another protein implicated in cell-cycle arrest) is normal
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• 24 hours after 2 Gy treatment the % of cleaved caspase-3-positive enteroids undergoing apoptosis is significantly higher than that in irradiated wild-type controls
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immune system
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• at 10 weeks of age, serum IL12p70 levels are significantly higher than in wild-type controls
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• at 10 weeks of age, serum IL2 levels are significantly higher than in wild-type controls
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• at 10 weeks of age, serum IL4 levels are significantly higher than in wild-type controls
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• at 10 weeks of age, IL12beta transcript levels are significantly increased in colonic tissue
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• at 10 weeks of age, mice exhibit higher serum levels of proinflammatory cytokines than wild-type controls, indicating a baseline mild inflammation
• however, no symptoms of spontaneous disease are observed up to 20 weeks of age
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homeostasis/metabolism
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• at 10 weeks of age, serum IL12p70 levels are significantly higher than in wild-type controls
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• at 10 weeks of age, serum IL2 levels are significantly higher than in wild-type controls
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• at 10 weeks of age, serum IL4 levels are significantly higher than in wild-type controls
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• at 3 days after challenge with a lethal dose (10 Gy) of total body irradiation (TBI), both sexes show significantly more body weight loss than TBI-treated wild-type controls
• however, no significant change in gut barrier permeability is observed 72 hours after TBI
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• after challenge with 10 Gy of TBI, mice show significantly reduced viability with a median survival of 5 days versus 8 days in TBI-treated wild-type controls
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cellular
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• in culture, 24 hours after 1 Gy treatment, enteroids show significantly higher expression of Cdkn1a (aka p21 or p21WAF1/CIP1) than wild-type enteroids
• however, expression of Cdkn2c (aka p18Ink4c, another protein implicated in cell-cycle arrest) is unaffected
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• 6 hours after 10 Gy TBI, 8-week old mice exhibit significantly more TUNEL+ apoptotic cells per intestinal crypt than similarly treated wild-type controls
• 72 hours after 10 Gy TBI, mice exhibit significantly more cleaved caspase-3-positive cells in the epithelium of the small intestine than similarly treated wild-type controls
• 96 hours after 10 Gy TBI, when mice approach 75% initial body weight, Bax expression is significantly increased in the small intestine, consistent with elevated apoptosis
• however, 96 hours after 10 Gy, Pcna transcript levels are unaffected indicating normal epithelial proliferation
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• 24 hours after 2 Gy treatment the % of cleaved caspase-3-positive enteroids undergoing apoptosis is significantly higher than that in irradiated wild-type controls
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mortality/aging
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• after challenge with 10 Gy of TBI, mice show significantly reduced viability with a median survival of 5 days versus 8 days in TBI-treated wild-type controls
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