Analysis Tools
mortality/aging
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• ~30% of homozygotes succumb to disease within 3 months of age
• death is correlated with anemia and gradual weight loss
• at >3 months of age, mortality is increased but never reaches 100%
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digestive/alimentary system
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• at 9 weeks, 59% of mice displaying colitis develop a high grade dysplasia of the colonic mucosa
(J:68476)
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• minimal epithelial hyperplasia at 3 weeks
• prominent epithelial hyperplasia at 3 months
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• colonic prolapse is observed in some older mutants
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• at 9 weeks, 13% of homozygotes have adenocarcinomas
• in 10-31 week old animals, there is a 65% incidence of colorectal carcinomas
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• 25% with colorectal adenocarcinomas at 3 months
• higher incidence of colorectal cancer at 6 months but no metastasis to lymph nodes
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• anemic and underweight homozygotes display enterocolitis involving the entire intestinal tract, duodenum, proximal jejunum, and proximal colon
(J:15222)
• inflammation was limited to the proximal colon under specific pathogen free conditions
(J:15222)
• spontaneous inflammatory bowel disease (IBD) develops by 5 weeks in some animals
(J:107077)
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• lymphocytes and small numbers of neutrophiles as infiltrates in the lamina propria of the cecum, ascending and transverse colon at three weeks
• multifocal lesions in all regions of the large intestine at three months
• occasional transmural inflammation and crypt abscesses at 3 months
• more ulcerations at 6 months
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• all Il10-null mice develop colitis by the age of 9 weeks in contrast to wild-type littermates
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• 8% with duodenitis at 3 months of age
• increased duodenitis at 6 months
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growth/size/body
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• 3 fold increase in alveolar bone loss at 30 weeks relative to mice at 6 and 16 weeks
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• although some homozygotes with slow disease progression show normal body weights up to 12 weeks of age, all homozygotes are eventually affected by weight loss
• at 7-11 weeks of age, most homozygotes display a ~30% weight reduction relative to wild-type controls
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• at 7-11 weeks of age, ~75% of homozygotes are growth retarded relative to wild-type controls
• growth retardation is first observed between 3 and 4 weeks of age
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hematopoietic system
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• reduced proliferative response of CD4+ cells to UVB irradiation
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• increases with time and IBD
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• increases with time and IBD
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• severely anemic homozygotes display a hyperproliferative myeloid compartment
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• at 7-11 weeks of age, ~90% of homozygotes exhibit anemia, most likely due to iron deficiency
• the observed anemia is most often defined as microcytic or normocytic and hypochromic
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• severely anemic homozygotes show complete depletion of eythroid cells in the bone marrow
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• at 7-11 weeks of age, ~90% of homozygotes display decreased erythrocyte numbers relative to wild-type controls
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• at 7-11 weeks of age, ~90% of homozygotes display a reduced hemoglobin concentration in circulating blood
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• homozygotes display up to a 2-fold elevation in leukocyte numbers due to an increase in granulocytes
(J:15222)
• elevated at 3 weeks and increasing with age
(J:35020)
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• double control levels in the lamina propria
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• elevated
• activated memory phenotype
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• severely anemic homozygotes display hypoplasia of the splenic red pulp
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• total IgE levels are more than 7-fold higher and serum levels of OVA-specific IgE more than 2-fold higher than in wild-type mice after ovalbumin challenge
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• OVA-specific IgG1 levels are higher in ovalbumin-sensitized mutants
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• OVA-specific IgG2a levels are higher in ovalbumin-sensitized mutants
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immune system
| N |
• at 4-6 weeks of age, young homozygotes exhibit normal CD4+ and CD8+ T subsets in thymus and spleen as well as normal B cell subsets in bone marrow, spleen and peritoneum relative to wild-type controls
(J:15222)
• young homozygotes show a normal antibody response to alpha (1-3)-dextrane, suggesting a normal B-1 cell subset in the peritoneum
(J:15222)
• young homozygotes display normal antibody production and development of B cell memory in response to T cell-dependent immunization with haptenated chicken gamma-globulin
(J:15222)
(J:107077)
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• increases with time and IBD
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• increases with time and IBD
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• severely anemic homozygotes display a hyperproliferative myeloid compartment
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• homozygotes display up to a 2-fold elevation in leukocyte numbers due to an increase in granulocytes
(J:15222)
• elevated at 3 weeks and increasing with age
(J:35020)
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• double control levels in the lamina propria
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• elevated
• activated memory phenotype
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• severely anemic homozygotes display hypoplasia of the splenic red pulp
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• reduced proliferative response of CD4+ cells to UVB irradiation
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• anemic and underweight homozygotes display enterocolitis involving the entire intestinal tract, duodenum, proximal jejunum, and proximal colon
(J:15222)
• inflammation was limited to the proximal colon under specific pathogen free conditions
(J:15222)
• spontaneous inflammatory bowel disease (IBD) develops by 5 weeks in some animals
(J:107077)
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• lymphocytes and small numbers of neutrophiles as infiltrates in the lamina propria of the cecum, ascending and transverse colon at three weeks
• multifocal lesions in all regions of the large intestine at three months
• occasional transmural inflammation and crypt abscesses at 3 months
• more ulcerations at 6 months
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• all Il10-null mice develop colitis by the age of 9 weeks in contrast to wild-type littermates
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• 8% with duodenitis at 3 months of age
• increased duodenitis at 6 months
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• total IgE levels are more than 7-fold higher and serum levels of OVA-specific IgE more than 2-fold higher than in wild-type mice after ovalbumin challenge
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• OVA-specific IgG1 levels are higher in ovalbumin-sensitized mutants
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• OVA-specific IgG2a levels are higher in ovalbumin-sensitized mutants
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• increased interferon gamma in the colon
(J:35020)
• IFNgamma is expressed in colon in mice with minor IBD symptoms
(J:107077)
• elevated amounts of IFN gamma produced by irradiated CD4+ cells
(J:125760)
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• increased IL 1 alpha, IL6, in the colon
(J:35020)
• reduced IL4 production by irradiated CD4+ cells
(J:35020)
• production of IL1 alpha is 3-4 times higher than controls 24 hours after LPS stimulation
(J:51636)
• Il-2, but not Il-1beta is expressed in colon in mice with minor IBD symptoms
(J:107077)
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• production of TNF alpha is 3-4 times higher than controls 24 hours after LPS stimulation
(J:51636)
• TNFalpha is expressed in colon in mice with minor IBD symptoms
(J:107077)
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• greater numbers of cells migrate to lymph nodes after hapten exposure
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• blockage of delayed-type hypertension by midrange UV radiation is prevented
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• enhanced contact hypersensitivity to FITC
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• upon infection with the nematode N. brasiliensis, homozygotes develop a Th1 response in addition to the expected nematode-induced Th2 response, as shown by a 5-fold increase in IFN-gamma levels in culture supernatants of Con A-stimulated spleen cells
• a similar increase in IFN-gamma production is found in cultures of anti-CD3-stimulated spleenic CD4+ T cells from nematode-infected homozygotes relative to infected controls
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• enterocolitis involving the entire intestinal tract, duodenum, proximal jejunum, and proximal colon
• inflammation was limited to the proximal colon under specific pathogen free conditions
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• upon infection with the nematode N. brasiliensis, homozygotes develop a Th1 response in addition to the expected nematode-induced Th2 response, as shown by a 5-fold increase in IFN-gamma levels in culture supernatants of Con A-stimulated spleen cells
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• time to death induced by exposure to Plasmodium falciparum is decreased compared to in wild-type mice (7+/-0 days compared to 7.8+/-0.2 days, respectively)
• in mice depleted of regulatory T cells, experimental cerebral malaria is delayed following exposure to Plasmodium falciparum but disease progression occurs unlike in wild-type mice similarly treated
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• significantly lower cardiac graft survival times
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neoplasm
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• at 9 weeks, 13% of homozygotes have adenocarcinomas
• in 10-31 week old animals, there is a 65% incidence of colorectal carcinomas
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• 25% with colorectal adenocarcinomas at 3 months
• higher incidence of colorectal cancer at 6 months but no metastasis to lymph nodes
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• CD8+ cells impart faster tumor rejection in hosts
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• do not develop skin tumors in response to UVB (280-350nm) exposure, even after 1 year
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respiratory system
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• mutants sensitized and challenged to ovalbumin (OVA) fail to develop airway hyper-responsiveness despite a significant eosinophilic airway inflammatory response
(J:62283)
• mutants are hyporesponsive to electrical field stimulation of trachea smooth muscle after OVA aerosol challenge
(J:62283)
• airway response to methacholine is reduced by 37%
(J:115459)
• tracheal rings are less responsive to KCl
(J:115459)
• less tension develops (restored by treatment with L-NAME)
(J:115459)
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homeostasis/metabolism
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• 90% more necrosis after experimental ischemia and reperfusion than found in controls
• 60% more polymorphonuclear neutrophiles per unit area in mid-ventricular slices relative to controls
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• exhaled NO is significantly decreased
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• plasma insulin levels are 55% lower than controls after an overnight fast following 6 weeks on a high fat diet
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• greater increase in insulin stimulated whole body glucose uptake when corrected for lower plasma insulin
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• homozygotes display depleted iron stores in spleen and bone marrow
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• homozygotes display a 50% reduction in serum iron levels relative to wild-type controls
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• decreased cholesterol esters
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• increased free cholesterol
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• basal free fatty acid levels are significantly increased
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• OVA-sensitized mutants exhibit higher eosinophil peroxidase and leukotriene levels in bronchoalveolar lavage fluid than wild-type mice
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• 54% increase in hepatic triglycerides relative to controls
• plasma triglycerides not elevated
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• increased phosphorylated protein kinase after insulin stimulation
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• higher levels of alanine:2-oxaloglutarate aminotransferase in plasma 8 hours after lipopolysaccharide treatment
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• reduced
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• increased interferon gamma in the colon
(J:35020)
• IFNgamma is expressed in colon in mice with minor IBD symptoms
(J:107077)
• elevated amounts of IFN gamma produced by irradiated CD4+ cells
(J:125760)
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• increased IL 1 alpha, IL6, in the colon
(J:35020)
• reduced IL4 production by irradiated CD4+ cells
(J:35020)
• production of IL1 alpha is 3-4 times higher than controls 24 hours after LPS stimulation
(J:51636)
• Il-2, but not Il-1beta is expressed in colon in mice with minor IBD symptoms
(J:107077)
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• production of TNF alpha is 3-4 times higher than controls 24 hours after LPS stimulation
(J:51636)
• TNFalpha is expressed in colon in mice with minor IBD symptoms
(J:107077)
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• airway response to methacholine is reduced by 37%
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• experimental wound is a 6 mm circular excision through the full thickness of the skin
• macroscopic wound closure is accelerated
• by day 3, density of vascular structures significantly increased
• earlier and more persistent influx of greater numbers of macrophage into wound
• fully epithelialized and scab lost by 7 days
• increased collagen content and advanced maturation and organization of collagen bundles at 14 days
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endocrine/exocrine glands
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• increases with time and IBD
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• increases with time and IBD
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behavior/neurological
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• latency to paw-licking is significantly longer on a hot plate test
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cardiovascular system
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• 26% increase in maternal blood space in the labyrinth
• fetal capillaries are normal
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• 90% more necrosis after experimental ischemia and reperfusion than found in controls
• 60% more polymorphonuclear neutrophiles per unit area in mid-ventricular slices relative to controls
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craniofacial
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• 3 fold increase in alveolar bone loss at 30 weeks relative to mice at 6 and 16 weeks
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embryo
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• 26% increase in maternal blood space in the labyrinth
• fetal capillaries are normal
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• 37% increase in cross-sectional area
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limbs/digits/tail
short femur
(
J:93577
)
liver/biliary system
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• 54% increase in hepatic triglycerides relative to controls
• plasma triglycerides not elevated
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• hepatic glucose production is reduced more than in controls
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• increased response in liver 4 hours after lipopolysaccharide treatment
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skeleton
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• 3 fold increase in alveolar bone loss at 30 weeks relative to mice at 6 and 16 weeks
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short femur
(
J:93577
)
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• decreased osteoblast generation in primary bone marrow stromal culture
• 40% fewer mineralized bone-like nodules in bone marrow cell culture
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• significantly reduced femoral ash weight
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• cortical bone mass reduced
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• reduced trabecular bone surface
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• reduced trabecular number
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• cancellous bone mass of the tibia significantly decreased
• trabecular bone further reduced in mice with colitis
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• reduced trabecular width
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• cancellous mineral apposition rate and bone formation rate are reduced
• bone resorption is normal
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• femora more fragile in mechanical load tests
• reduced stiffness of femora
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cellular
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• increased response in liver 4 hours after lipopolysaccharide treatment
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• decreased osteoblast generation in primary bone marrow stromal culture
• 40% fewer mineralized bone-like nodules in bone marrow cell culture
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• reduced proliferative response of CD4+ cells to UVB irradiation
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| inflammatory bowel disease | DOID:0050589 |
OMIM:PS266600 |
J:15222 , J:35020 | |
