Analysis Tools
cellular
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• in culture, CD4+ T cells isolated from spleen are hypersensitive to anti-CD3 plus anti-CD28 stimulated proliferation, as measured by 3H-thymidine incorporation
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immune system
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• increased CD4+ T cell number in spleen at 12-14 months of age
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• increased CD8+ T cell number in spleen at 12-14 months of age
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• decreased number of Foxp3+CD4+ Treg cells in spleen at 12-14 months of age
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• increased plasma IgG3 levels at 12 months of age, consistent with increased T cell-derived IL-17 levels
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• at 12-14 months of age, mice exhibit an increase in CD44+ active T cells and a decrease in CD62L+ naive T cells, suggesting that T cells are hyperactivated
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• in culture, CD4+ T cells isolated from spleen are hypersensitive to anti-CD3 plus anti-CD28 stimulated proliferation, as measured by 3H-thymidine incorporation
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• increased plasma MCP-1 levels at 12-14 months of age
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• increased plasma interferon-gamma levels at 12-14 months of age
• plasma interferon-gamma levels are somewhat reduced at 24 h of rapamycin treatment and return to basal (pre-treatment) levels after 2 weeks of rapamycin treatment, similar to what is observed in wild-type controls
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• increased plasma IL-10 levels at 12-14 months of age
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• increased plasma IL-12 levels at 12-14 months of age
• plasma IL-12(p70) levels are not significantly altered in response to rapamycin treatment, similar to what is observed in wild-type controls
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• increased plasma levels of IL-12(p40) levels at 12-14 months of age
• plasma levels of IL-12(p40) are reduced to wild-type levels at 24 h of rapamycin treatment and remain suppressed after 2 weeks of treatment; in contrast, rapamycin has no significant effect on plasma IL-12(p40) in wild-type controls
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• increased plasma IL-2 levels at 12-14 months of age
• plasma IL-2 levels are not significantly altered in response to rapamycin treatment, similar to what is observed in wild-type controls
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• increased plasma IL-4 levels at 12-14 months of age
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• increased interferon-gamma secretion by CD4+ T cells isolated from spleen
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• increased IL-17 secretion by CD4+ T cells isolated from spleen
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• ratio of immune infiltrates per total area is significantly increased in liver tissue, indicating chronic inflammation without a specific trigger such as infection or injury
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• mice develop enhanced immune responses resulting in autoimmunity
• mammalian target of rapamycin complex 1 (mTORC1) signaling is highly activated in several tissues
• hyperimmune phenotype can be partially ameliorated by treatment with rapamycin, the allosteric mTORC1 inhibitor
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• immune cell infiltration in the intestine at 12-14 months of age
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• immune cell infiltration in the salivary gland at 12-14 months of age
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• immune cell infiltration in the liver at 12-14 months of age
• infiltrating immune cells in liver tissue are predominantly CD3+ T cells and B220+ B cells
• ratio of immune infiltrates per total area is significantly increased in liver tissue, indicating chronic inflammation
• area of immune infiltrates in liver is dramatically reduced after 2 weeks of rapamycin treatment
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• immune cell infiltration in the kidney at 12-14 months of age
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• immune cell infiltration in the lungs at 12-14 months of age
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homeostasis/metabolism
| N |
• mice do not exhibit enhanced insulin sensitivity and are not protected from obesity on a high-fat diet
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• increased plasma VEGF levels at 12-14 months of age
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• increased plasma MCP-1 levels at 12-14 months of age
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• increased plasma interferon-gamma levels at 12-14 months of age
• plasma interferon-gamma levels are somewhat reduced at 24 h of rapamycin treatment and return to basal (pre-treatment) levels after 2 weeks of rapamycin treatment, similar to what is observed in wild-type controls
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• increased plasma IL-10 levels at 12-14 months of age
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• increased plasma IL-12 levels at 12-14 months of age
• plasma IL-12(p70) levels are not significantly altered in response to rapamycin treatment, similar to what is observed in wild-type controls
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• increased plasma levels of IL-12(p40) levels at 12-14 months of age
• plasma levels of IL-12(p40) are reduced to wild-type levels at 24 h of rapamycin treatment and remain suppressed after 2 weeks of treatment; in contrast, rapamycin has no significant effect on plasma IL-12(p40) in wild-type controls
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• increased plasma IL-2 levels at 12-14 months of age
• plasma IL-2 levels are not significantly altered in response to rapamycin treatment, similar to what is observed in wild-type controls
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• increased plasma IL-4 levels at 12-14 months of age
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• increased plasma aspartate transaminase (AST) levels at 12 months of age
• however, plasma alanine transaminase (ALT) levels are normal
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• decreased blood urea nitrogen levels at 12 months of age
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hematopoietic system
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• increased CD4+ T cell number in spleen at 12-14 months of age
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• increased CD8+ T cell number in spleen at 12-14 months of age
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• decreased number of Foxp3+CD4+ Treg cells in spleen at 12-14 months of age
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• increased plasma IgG3 levels at 12 months of age, consistent with increased T cell-derived IL-17 levels
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• at 12-14 months of age, mice exhibit an increase in CD44+ active T cells and a decrease in CD62L+ naive T cells, suggesting that T cells are hyperactivated
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• in culture, CD4+ T cells isolated from spleen are hypersensitive to anti-CD3 plus anti-CD28 stimulated proliferation, as measured by 3H-thymidine incorporation
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liver/biliary system
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• immune cell infiltration in the liver at 12-14 months of age
• infiltrating immune cells in liver tissue are predominantly CD3+ T cells and B220+ B cells
• ratio of immune infiltrates per total area is significantly increased in liver tissue, indicating chronic inflammation
• area of immune infiltrates in liver is dramatically reduced after 2 weeks of rapamycin treatment
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pale liver
(
J:234283
)
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• pale livers are occasionally seen in mice at >12 months of age
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digestive/alimentary system
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• immune cell infiltration in the intestine at 12-14 months of age
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• immune cell infiltration in the salivary gland at 12-14 months of age
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renal/urinary system
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• immune cell infiltration in the kidney at 12-14 months of age
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respiratory system
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• immune cell infiltration in the lungs at 12-14 months of age
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endocrine/exocrine glands
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• immune cell infiltration in the salivary gland at 12-14 months of age
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growth/size/body
| N |
• mice develop normally and grow into adulthood with no obvious growth abnormalities
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