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Phenotypes Associated with This Genotype
Genotype
MGI:2665845
Allelic
Composition
Il10tm1Cgn/Il10tm1Cgn
Genetic
Background
involves: 129P2/OlaHsd * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Il10tm1Cgn mutation (14 available); any Il10 mutation (31 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• ~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%

digestive/alimentary system
• at 9 weeks, 59% of mice displaying colitis develop a high grade dysplasia of the colonic mucosa (J:68476)
• minimal epithelial hyperplasia at 3 weeks
• prominent epithelial hyperplasia at 3 months
• colonic prolapse is observed in some older mutants
• at 9 weeks, 13% of homozygotes have adenocarcinomas
• in 10-31 week old animals, there is a 65% incidence of colorectal carcinomas
• 25% with colorectal adenocarcinomas at 3 months
• higher incidence of colorectal cancer at 6 months but no metastasis to lymph nodes
• 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)
• 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
• all Il10-null mice develop colitis by the age of 9 weeks in contrast to wild-type littermates
• 8% with duodenitis at 3 months of age
• increased duodenitis at 6 months

growth/size/body
• 3 fold increase in alveolar bone loss at 30 weeks relative to mice at 6 and 16 weeks
• 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
• 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

hematopoietic system
• reduced proliferative response of CD4+ cells to UVB irradiation
• increases with time and IBD
• increases with time and IBD
• severely anemic homozygotes display a hyperproliferative myeloid compartment
• 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
• severely anemic homozygotes show complete depletion of eythroid cells in the bone marrow
• at 7-11 weeks of age, ~90% of homozygotes display decreased erythrocyte numbers relative to wild-type controls
• at 7-11 weeks of age, ~90% of homozygotes display a reduced hemoglobin concentration in circulating blood
• 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)
• double control levels in the lamina propria
• elevated
• activated memory phenotype
• severely anemic homozygotes display hypoplasia of the splenic red pulp
• 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
• OVA-specific IgG1 levels are higher in ovalbumin-sensitized mutants
• OVA-specific IgG2a levels are higher in ovalbumin-sensitized mutants

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)
• increases with time and IBD
• increases with time and IBD
• severely anemic homozygotes display a hyperproliferative myeloid compartment
• 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)
• double control levels in the lamina propria
• elevated
• activated memory phenotype
• severely anemic homozygotes display hypoplasia of the splenic red pulp
• reduced proliferative response of CD4+ cells to UVB irradiation
• 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)
• 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
• all Il10-null mice develop colitis by the age of 9 weeks in contrast to wild-type littermates
• 8% with duodenitis at 3 months of age
• increased duodenitis at 6 months
• 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
• OVA-specific IgG1 levels are higher in ovalbumin-sensitized mutants
• OVA-specific IgG2a levels are higher in ovalbumin-sensitized mutants
• 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)
• 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)
• increased TNF alpha in the colon (J:35020)
• 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)
• greater numbers of cells migrate to lymph nodes after hapten exposure
• blockage of delayed-type hypertension by midrange UV radiation is prevented
• enhanced contact hypersensitivity to FITC
• 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
• enterocolitis involving the entire intestinal tract, duodenum, proximal jejunum, and proximal colon
• inflammation was limited to the proximal colon under specific pathogen free conditions
• 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
• 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
• significantly lower cardiac graft survival times

neoplasm
• at 9 weeks, 13% of homozygotes have adenocarcinomas
• in 10-31 week old animals, there is a 65% incidence of colorectal carcinomas
• 25% with colorectal adenocarcinomas at 3 months
• higher incidence of colorectal cancer at 6 months but no metastasis to lymph nodes
• CD8+ cells impart faster tumor rejection in hosts
• do not develop skin tumors in response to UVB (280-350nm) exposure, even after 1 year

respiratory system
• 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)

homeostasis/metabolism
• 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
• exhaled NO is significantly decreased
• plasma insulin levels are 55% lower than controls after an overnight fast following 6 weeks on a high fat diet
• greater increase in insulin stimulated whole body glucose uptake when corrected for lower plasma insulin
• homozygotes display depleted iron stores in spleen and bone marrow
• homozygotes display a 50% reduction in serum iron levels relative to wild-type controls
• decreased cholesterol esters
• increased free cholesterol
• basal free fatty acid levels are significantly increased
• OVA-sensitized mutants exhibit higher eosinophil peroxidase and leukotriene levels in bronchoalveolar lavage fluid than wild-type mice
• 54% increase in hepatic triglycerides relative to controls
• plasma triglycerides not elevated
• increased phosphorylated protein kinase after insulin stimulation
• higher levels of alanine:2-oxaloglutarate aminotransferase in plasma 8 hours after lipopolysaccharide treatment
• 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)
• 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)
• increased TNF alpha in the colon (J:35020)
• 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)
• airway response to methacholine is reduced by 37%
• 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

endocrine/exocrine glands
• increases with time and IBD
• increases with time and IBD

behavior/neurological
• latency to paw-licking is significantly longer on a hot plate test

cardiovascular system
• 26% increase in maternal blood space in the labyrinth
• fetal capillaries are normal
• 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

craniofacial
• 3 fold increase in alveolar bone loss at 30 weeks relative to mice at 6 and 16 weeks

embryo
• 26% increase in maternal blood space in the labyrinth
• fetal capillaries are normal
• 37% increase in cross-sectional area

limbs/digits/tail

liver/biliary system
• 54% increase in hepatic triglycerides relative to controls
• plasma triglycerides not elevated
• hepatic glucose production is reduced more than in controls
• increased response in liver 4 hours after lipopolysaccharide treatment

skeleton
• 3 fold increase in alveolar bone loss at 30 weeks relative to mice at 6 and 16 weeks
• decreased osteoblast generation in primary bone marrow stromal culture
• 40% fewer mineralized bone-like nodules in bone marrow cell culture
• significantly reduced femoral ash weight
• cortical bone mass reduced
• reduced trabecular bone surface
• reduced trabecular number
• cancellous bone mass of the tibia significantly decreased
• trabecular bone further reduced in mice with colitis
• reduced trabecular width
• cancellous mineral apposition rate and bone formation rate are reduced
• bone resorption is normal
• femora more fragile in mechanical load tests
• reduced stiffness of femora

integument
• latency to paw-licking is significantly longer on a hot plate test

cellular
• increased response in liver 4 hours after lipopolysaccharide treatment
• decreased osteoblast generation in primary bone marrow stromal culture
• 40% fewer mineralized bone-like nodules in bone marrow cell culture
• reduced proliferative response of CD4+ cells to UVB irradiation

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
inflammatory bowel disease DOID:0050589 OMIM:PS266600
J:15222 , J:35020


Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB), Gene Ontology (GO)
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last database update
08/13/2019
MGI 6.14
The Jackson Laboratory