digestive/alimentary system
• 80% of double null animals develop rectal prolapse; seen at 5 weeks of age and beyond
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• mice develop spontaneous inflammatory bowel disease (IBD) involving the entire intestinal tract
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immune system
• thymocytes are more susceptible to apoptosis than in single null mice (10% of total cells are apoptotic vs 1%)
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• CD4+ and CD8+ T cells show reduced proliferative capacity compared to those of single null or wild-type mice when stimulated with anti-CD3 antibodies
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• mice develop spontaneous inflammatory bowel disease (IBD) involving the entire intestinal tract
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• animals with progressive disease have thymuses with no clear corticomedullary demarcation, scattered cortical cells and accumulation of thymocytes in medulla
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• thymus cellularity declines rapidly as mice develop IBD
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• accelerated in animals with severe IBD
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• spleens are 2-fold larger than in single null or wild-type mice
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• circulating neutrophil numbers are 4-fold higher than in single null or wild-type mice with IBD
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• lymphocyte cell counts are 2-fold lower than in single null or wild-type mice with IBD
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• F4/80/CD11 macrophages are more numerous than in spleens of single null or wild-type mice with IBD
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• red pulp is expanded and congested with accumulation of red blood cells with IBD
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• there is almost complete absence of white pulp in spleens of double null mice with IBD
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• overall cellularity is reduced, with about 50% of CD4+, CD8+, and B cell numbers in single null or wild-type mice
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• CD4+ T cells have a memory phenotype with high expression of CD44 and low expression of CD62L, while T cells from single null and wild-type mice have a nae phenotype
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• 2-3-fold higher mRNA levels of Il-1beta, Il-2, TNFalpha and IFNgamma than found in single null mice are detected in colons; Il-12p35 and p40 are detected in double null colons, but not in single mutants
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• MLN are 3- to 4-fold higher; cell numbers are increased relative to other lines of mice
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• absolute numbers of CD4+ and CD8+ T cells are 3-fold higher in mesenteric lymph nodes (MLN)
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hematopoietic system
• thymocytes are more susceptible to apoptosis than in single null mice (10% of total cells are apoptotic vs 1%)
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• CD4+ and CD8+ T cells show reduced proliferative capacity compared to those of single null or wild-type mice when stimulated with anti-CD3 antibodies
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• animals with progressive disease have thymuses with no clear corticomedullary demarcation, scattered cortical cells and accumulation of thymocytes in medulla
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• thymus cellularity declines rapidly as mice develop IBD
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• accelerated in animals with severe IBD
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• spleens are 2-fold larger than in single null or wild-type mice
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• mice have decreased erythrocyte numbers and lower hemoglobin concentrations than single null or wild-type mice with IBD
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• circulating neutrophil numbers are 4-fold higher than in single null or wild-type mice with IBD
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• lymphocyte cell counts are 2-fold lower than in single null or wild-type mice with IBD
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• F4/80/CD11 macrophages are more numerous than in spleens of single null or wild-type mice with IBD
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• red pulp is expanded and congested with accumulation of red blood cells with IBD
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• there is almost complete absence of white pulp in spleens of double null mice with IBD
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• overall cellularity is reduced, with about 50% of CD4+, CD8+, and B cell numbers in single null or wild-type mice
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• CD4+ T cells have a memory phenotype with high expression of CD44 and low expression of CD62L, while T cells from single null and wild-type mice have a nae phenotype
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homeostasis/metabolism
• 2-3-fold higher mRNA levels of Il-1beta, Il-2, TNFalpha and IFNgamma than found in single null mice are detected in colons; Il-12p35 and p40 are detected in double null colons, but not in single mutants
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cellular
• thymocytes are more susceptible to apoptosis than in single null mice (10% of total cells are apoptotic vs 1%)
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• CD4+ and CD8+ T cells show reduced proliferative capacity compared to those of single null or wild-type mice when stimulated with anti-CD3 antibodies
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endocrine/exocrine glands
• animals with progressive disease have thymuses with no clear corticomedullary demarcation, scattered cortical cells and accumulation of thymocytes in medulla
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• thymus cellularity declines rapidly as mice develop IBD
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• accelerated in animals with severe IBD
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growth/size/body
• spleens are 2-fold larger than in single null or wild-type mice
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