|
Allele Symbol Allele Name Allele ID |
Il10tm1Cgn targeted mutation 1, University of Cologne MGI:1857199 |
| Summary |
22 genotypes |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• LPS treatment markedly impairs contractions of the carotid artery induced by the thromboxane analogue U46619 and by phenylephrine
|
|
• LPS treatment markedly impairs contractions of the carotid artery induced by the thromboxane analogue U46619 and by phenylephrine
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• decrease in survival times of heart transplants from BALB/c mice after a 30 day course of anti-CD4 and anti-CD8 mAb
• acute rejection severity of cardiac allografts (BALB/c) is increased compared to wild-type controls
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• PGE2 represses LPS induction to a lesser extent than it does in controls
|
|
• PGE2 represses LPS induction to a lesser extent than it does in controls
|
|
• PGE2 represses LPS induction to a lesser extent than it does in controls
|
|
• PGE2 represses LPS induction to a lesser extent than it does in controls
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Characterization of Il10tm1Cgn/Il10tm1Cgn mice
|
• lower body weight gain between 5 and 10 weeks of age than for controls
|
|
• mutants develop severe inflammation in the colon leading to inflammatory bowel disease
|
|
• upon DSS exposure
|
|
• mice infected with T. muris exhibit increased worm burden and cecum score compared with similarly treated wild-type mice
|
|
• CD25-positive CD4 T cells from these mice fail to protect against the wasting disease induced by transferring nave CD4 T cells into immunodeficient hosts
• however, CD25-postive CD4 T cells inhibit the expansion of naive T cells in Rag2 deficient hosts as effectively as wild-type CD25-positive CD4 T cells
|
|
• levels of cytokines increase in the brain are greater than for controls after lipopolysaccharide treatment
(J:139972)
• in LPS-injected mice
(J:157787)
|
|
• in LPS-injected mice
|
|
• in LPS-injected mice
|
|
• plasma levels remain elevated for 24 hours after lipopolysaccharide treatment as opposed to 4 hours for controls
(J:139972)
• in LPS-injected mice
(J:157787)
|
|
• in LPS-injected mice
|
|
• in LPS-injected mice
|
|
• in LPS-injected mice
|
|
• plasma levels remain elevated for 24 hours after lipopolysaccharide treatment as opposed to 4 hours for controls
(J:139972)
• slightly in LPS-injected mice
(J:157787)
|
|
• in LPS-injected mice
|
|
• LPS-injected mice exhibit increased CXCL10 and CXCL1 levels compared with similarly treated wild-type mice
|
|
• mice infected with T. muris exhibit increased worm burden and cecum score compared with similarly treated wild-type mice
|
|
• time to fatigue on a motorized treadmill is reduced 24% after lipopolysaccharide treatment
|
|
• increased toxicity of N-methyl-D-aspartate in primary neuron culture
|
|
• lipopolysaccharide causes a very significant drop in core body temperature
|
|
• levels of cytokines increase in the brain are greater than for controls after lipopolysaccharide treatment
(J:139972)
• in LPS-injected mice
(J:157787)
|
|
• in LPS-injected mice
|
|
• in LPS-injected mice
|
|
• plasma levels remain elevated for 24 hours after lipopolysaccharide treatment as opposed to 4 hours for controls
(J:139972)
• in LPS-injected mice
(J:157787)
|
|
• in LPS-injected mice
|
|
• in LPS-injected mice
|
|
• in LPS-injected mice
|
|
• plasma levels remain elevated for 24 hours after lipopolysaccharide treatment as opposed to 4 hours for controls
(J:139972)
• slightly in LPS-injected mice
(J:157787)
|
|
• in LPS-injected mice
|
|
• LPS-injected mice exhibit increased CXCL10 and CXCL1 levels compared with similarly treated wild-type mice
|
|
• lesion volume after middle cerebral artery occlusion increases 30%
|
|
• rectal prolapse is seen at a median time of 16 weeks of age
|
|
• 20% of mutants with colonic inflammation exhibit colon tumors; tumors are adenocarcinomas
• tumors develop between 25 and 35 weeks of age
|
|
• mutants develop severe inflammation in the colon leading to inflammatory bowel disease
|
|
• upon DSS exposure
|
|
• mice infected with T. muris exhibit increased worm burden and cecum score compared with similarly treated wild-type mice
|
|
• reduced choroidal neovascularization 7 days following krypton laser exposure of the eye
|
|
• lower under basal conditions
|
|
• LPS treatment markedly impairs contractions of the carotid artery induced by the thromboxane analogue U46619 and by phenylephrine
|
|
• endothelin 1 induced contraction of Aorta and first order mesenteric arteries is greater than controls when also treated with L-NAME and indomethecine and TNFalpha
• response to endothelin 1 is eliminated in the presence of PD-98059
|
|
• LPS treatment markedly impairs contractions of the carotid artery induced by the thromboxane analogue U46619 and by phenylephrine
|
|
• endothelin 1 induced contraction of Aorta and first order mesenteric arteries is greater than controls when also treated with L-NAME and indomethecine and TNFalpha
• response to endothelin 1 is eliminated in the presence of PD-98059
|
|
• rotarod performance worsens after IP lipopolysaccharide injection
• effect persists at least 24 hours
• performance fails to improve over consecutive trials but only after IP lipopolysaccharide injection
|
|
• more time in "slow-wave sleep" and less time awake during dark phase
• less effect of influenza virus infection on slow wave sleep during dark phase but a greater decrease in delta wave amplitude
• lipopolysaccharide causes an overall decrease in delta wave amplitude
• lipopolysaccharide causes decreased slow wave and REM sleep during light phase
• lipopolysaccharide results in increased time spent awake, particularly in light phase
|
|
• time to fatigue on a motorized treadmill is reduced 24% after lipopolysaccharide treatment
|
|
• lesion volume after middle cerebral artery occlusion increases 30%
|
|
• increased sensitivity to oxygen or glucose deprivation
|
|
• increased toxicity of N-methyl-D-aspartate in primary neuron culture
|
|
• reduced choroidal neovascularization 7 days following krypton laser exposure of the eye
|
|
• 20% of mutants with colonic inflammation exhibit colon tumors; tumors are adenocarcinomas
• tumors develop between 25 and 35 weeks of age
|
|
• increased toxicity of N-methyl-D-aspartate in primary neuron culture
|
|
• CD25-positive CD4 T cells from these mice fail to protect against the wasting disease induced by transferring nave CD4 T cells into immunodeficient hosts
• however, CD25-postive CD4 T cells inhibit the expansion of naive T cells in Rag2 deficient hosts as effectively as wild-type CD25-positive CD4 T cells
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| inflammatory bowel disease | DOID:0050589 |
OMIM:PS266600 |
J:124308 , J:149347 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice treated with Gal1 exhibit less protection from stress-induced fetal loss compared to similarly treated wild-type mice
|
|
• in LPS-treated mice
|
|
• in LPS-treated mice
|
|
• 6 hours after LPS injection, TNF, Il12 and Ifng levels are substantially higher than in controls
|
|
• after three subcutaneous injections of LPS into the flank, mice develop solid subcutaneous swellings whereas wild-type do not
• lesion is associated with infiltration of macrophages and neutrophils, edema, and extensive necrosis of dermal, epidermal, and muscle layers of skin
• 5 days after flank injection of CpG, mice develop solid subcutaneous swellings at the injection site; lesions show conspicuous edema, massive infiltration by macrophages and neutrophilic granulocytes, and extensive necrosis of the dermis, epidermis and muscle layer of the skin while lesions in controls do not display edema or necrosis and show infiltration by macrophages primarily
|
|
• mice show exaggerated inflammatory response upon exposure to CML-mps-containing eluate compared to control
|
|
• i.p. injection of LPS results in death in all animal by 48 hours, compared to survival of 23/25 controls
(J:117122)
• LPS-treated mice exhibit uncontrollable release of IL12 and TNF-alpha compared with wild-type mice
(J:118833)
|
|
• 7% of mutants develop rectal prolapse at 16 weeks of age
|
|
• mice show exaggerated inflammatory response upon exposure to CML-mps-containing eluate compared to control
|
|
• in LPS-treated mice
|
|
• in LPS-treated mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice older than 4 weeks weigh significantly less than controls
|
|
• increased colon permeability to mannitol at 2, 4, and 10weeks but not under germ free conditions
• ileal permeability to mannitol 3X higher than in controls at 2 weeks but normal at 6 weeks
• more IFNgamma and TNFalpha produced in the ileum and colon than in controls
• colonic iNOS production increases with age after 4 weeks
|
|
• mild colitis at 4 weeks which plateaus by 8 weeks
• no ileal injury through 16 weeks
• no colitis when raised in germ free conditions
|
|
• mild colitis at 4 weeks which plateaus by 8 weeks
• no ileal injury through 16 weeks
• no colitis when raised in germ free conditions
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• ~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%
|
|
• 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
|
|
• 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
|
|
• 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
|
| 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)
|
|
• 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
|
|
• 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
|
|
• 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)
|
|
• 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
|
|
• reduced
|
|
• 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)
|
|
• 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
|
|
• increases with time and IBD
|
|
• increases with time and IBD
|
|
• latency to paw-licking is significantly longer on a hot plate test
|
|
• 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
|
|
• 3 fold increase in alveolar bone loss at 30 weeks relative to mice at 6 and 16 weeks
|
|
• 26% increase in maternal blood space in the labyrinth
• fetal capillaries are normal
|
|
• 37% increase in cross-sectional area
|
|
• 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
|
|
• 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
|
|
• 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 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• lower body weight than controls
|
|
• increased lymphocytes in the lamina propria
• inflamatory cells in the mucosa
• epithelial hyperplasia
• reduced mucin producing goblet cells
|
|
• increased lymphocytes in the lamina propria
• inflamatory cells in the mucosa
• epithelial hyperplasia
• reduced mucin producing goblet cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 100% of mice develop rectal prolapse by approximately 75 days
|
|
• increase in levels of fecal bacteria as compared to Il10 mutation alone
|
|
• severe uniform colitis in 100% of mice; presence of intestinal endothelial cell (IEC)-specific Tlr5 null mutation exacerbates phenotype
• increased incidence of rectal prolapse; presence of IEC-specific Tlr5 null mutation exacerbates phenotype
|
|
• severe uniform colitis in 100% of mice; presence of intestinal endothelial cell (IEC)-specific Tlr5 null mutation exacerbates phenotype
• increased incidence of rectal prolapse; presence of IEC-specific Tlr5 null mutation exacerbates phenotype
|
|
• mice are euthanized due to rectal prolapse
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• there is no IL-10 secretion from bone marrow derived macrophages after LPS stimulation
|
|
• LPS stimulation of bone marrow derived macrophages leads to higher secretion of IL12a than in controls during an 8 hour time period
|
|
• LPS stimulation of bone marrow derived macrophages leads to higher secretion of IL12b than in controls during an 8 hour time period
|
|
• LPS stimulation of bone marrow derived macrophages leads to higher secretion of IL-6 than in controls during an 8 hour time period
|
|
• LPS stimulation of bone marrow derived macrophages leads to higher secretion of TNF than in controls during an 8 hour time period
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• rectal prolapse is seen at a median time of 11 weeks of age
|
|
• 88% of mutants with colonic inflammation exhibit colon tumors; majority of tumors are invasive adenocarcinomas
• mutants exhibit a higher tumor burden (3-4 tumors per colon on average) than single Il10 homozygotes (1 tumor per colon)
• tumors develop as early as 8-12 weeks of age
|
|
• mutants develop segmental, patchy colon inflammation with areas of healthy-appearing colon adjacent to areas of severe inflammation
• mutants exhibit higher total colonic inflammation at 5-6 weeks of age than single Il10 homozygotes and show fewer fields of no inflammation
• neutrophils are the dominant cellular infiltrate in the colon which are not seen in the single Il10 homozygote
• mutants develop progressive inflammatory bowel disease much earlier than single Il10 homozygotes
|
|
• mutants develop segmental, patchy colon inflammation with areas of healthy-appearing colon adjacent to areas of severe inflammation
• mutants exhibit higher total colonic inflammation at 5-6 weeks of age than single Il10 homozygotes and show fewer fields of no inflammation
• neutrophils are the dominant cellular infiltrate in the colon which are not seen in the single Il10 homozygote
• mutants develop progressive inflammatory bowel disease much earlier than single Il10 homozygotes
|
|
• 88% of mutants with colonic inflammation exhibit colon tumors; majority of tumors are invasive adenocarcinomas
• mutants exhibit a higher tumor burden (3-4 tumors per colon on average) than single Il10 homozygotes (1 tumor per colon)
• tumors develop as early as 8-12 weeks of age
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| colorectal cancer | DOID:9256 |
OMIM:114500 |
J:149347 | |
| inflammatory bowel disease | DOID:0050589 |
OMIM:PS266600 |
J:149347 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice exhibit enhanced Th2 responses after infection with S. mansoni eggs compared to controls
|
|
• mice exhibit enhanced Th2 responses after infection with S. mansoni eggs compared to controls
|
|
• there is a 200- to 250-fold increase in IL-13 mRNA present in the lungs after infection with S. mansoni eggs
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 80% of double null animals develop rectal prolapse; seen at 5 weeks of age and beyond
|
|
• mice develop spontaneous inflammatory bowel disease (IBD) involving the entire intestinal tract
|
|
• thymocytes are more susceptible to apoptosis than in single null mice (10% of total cells are apoptotic vs 1%)
|
|
• 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
|
|
• mice develop spontaneous inflammatory bowel disease (IBD) involving the entire intestinal tract
|
|
• animals with progressive disease have thymuses with no clear corticomedullary demarcation, scattered cortical cells and accumulation of thymocytes in medulla
|
|
• thymus cellularity declines rapidly as mice develop IBD
|
|
• accelerated in animals with severe IBD
|
|
• spleens are 2-fold larger than in single null or wild-type mice
|
|
• 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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• 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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• 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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• 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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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• IL-12b (IL-12p40) production from activated macrophages is increased compared to single mutants
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• colon length is shorter
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• 50% of mutants develop rectal prolapse by 5 weeks of age
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• 120% more necrosis after experimental ischemia and reperfusion than found in controls
• 72% more polymorphonuclear neutrophiles per unit area in mid-ventricular slices relative to controls
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• 120% more necrosis after experimental ischemia and reperfusion than found in controls
• 72% more polymorphonuclear neutrophiles per unit area in mid-ventricular slices relative to controls
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• lesion development substantially increased at 16 weeks relative to Apoetm1Unc alone
• lesion size about 10 fold greater at 48 weeks than at 16 weeks but similar to controls
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• shift in cholesterol from VLDL to LDL
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• shift in cholesterol from VLDL to LDL
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• at 48 weeks
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• elevated at both 16 and 48 weeks
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• increased thrombin formation
• enhanced thrombotic response to injected thrombin
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• intracoronary platelet thrombi are significantly more frequent
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• at 48 weeks
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• elevated at both 16 and 48 weeks
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• compared with Il10tm1Cgn homozygotes
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• helminth-induced colitis compared with similarly treated Il10tm1Cgn homozygotes
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• mice exhibit lower Th1 response compared with Il10tm1Cgn homozygotes
• helminth-infected mice exhibit a decrease in Th1 response and an increase in Th2 response compared with similarly treated Il10tm1Cgn homozygotes
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• helminth-infected mice exhibit a decrease in Th1 response and an increase in Th2 response compared with similarly treated Il10tm1Cgn homozygotes
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• in stimulated lymphocytes
• in mesenteric lymph node cells from helminth-infected mice compared with similarly treated Il10tm1Cgn homozygotes
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• in mesenteric lymph node cells from helminth-infected mice compared with similarly treated Il10tm1Cgn homozygotes
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• helminth-induced colitis compared with similarly treated Il10tm1Cgn homozygotes
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• mice exhibit lower Th1 response compared with Il10tm1Cgn homozygotes
• helminth-infected mice exhibit a decrease in Th1 response and an increase in Th2 response compared with similarly treated Il10tm1Cgn homozygotes
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• helminth-infected mice exhibit a decrease in Th1 response and an increase in Th2 response compared with similarly treated Il10tm1Cgn homozygotes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice exhibit enhanced Th1 responses after infection with S. mansoni eggs compared to controls
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• there is a 75-fold increase in IFN-gamma mRNA in the lungs after infection with S. mansoni eggs
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• mice exhibit enhanced Th1 responses after infection with S. mansoni eggs compared to controls
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• most mice develop rectal prolapse by 150 days
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• severe colitis in 100% of mice; phenotype is less severe than in the presence of the intestinal endothelial cell (IEC)-specific Tlr5 null mutation
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• severe colitis in 100% of mice; phenotype is less severe than in the presence of the intestinal endothelial cell (IEC)-specific Tlr5 null mutation
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• mice are euthanized by 5 months due to rectal prolapse
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• normal until 24 weeks of age when they start losing weight
• life span normal in spite of weight loss
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• only small areas of inflammation in the mucosa
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• histology of two homozygotes at 34 weeks of age found severe Purkinje cell loss
|
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• double homozygous mothers on the NOD background often develop rectal prolapse after bearing 1 to 3 litters
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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 04/30/2024 MGI 6.23 |
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