Phenotypes associated with this allele

• Allele Symbol: Il10rb^tm1Agt
• Allele Name: targeted mutation 1, Michael Aguet
• Allele ID: MGI:2182946
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Il10rb^tm1Agt/Il10rb^tm1Agt	involves: 129S2/SvPas * C57BL/6	MGI:3603437
cx2	Il10rb^tm1Agt/Il10rb^tm1Agt Tg(Cd4-TGFBR2)16Flv/?	involves: 129S2/SvPas * C3H * C57BL/6	MGI:3789685

Genotype
MGI:3603437

hm1

• Allelic Composition: Il10rb^tm1Agt/Il10rb^tm1Agt
• Genetic Background: involves: 129S2/SvPas * C57BL/6

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

immune system

abnormal granulocyte differentiation ( J:45917 )

• increased granulocytopoiesis in sternal bone marrow

large intestinal inflammation ( J:45917 )

• mixed inflammatory cell mucosal inflammation in the large intestine

• predominantly involves macrophage, neutrophiles and T lymphocytes

colitis ( J:134156 )

• colitis is observed in mice 3-4 months of age with ulcerations found near the iliel-cecal junction, the ascending-to-descending colon transition and the anal-rectal junction

increased leukocyte cell number ( J:45917 )

• peripheral leukocytosis involving neutrophiles and monocytes

abnormal spleen morphology ( J:45917 )

increased spleen weight ( J:45917 )

• 4 fold increase in the spleen/body weight ratio

spleen hyperplasia ( J:45917 )

• increased numbers of splenocytes

abnormal mesenteric lymph node morphology ( J:45917 )

• mesenteric lymphadenopathy

abnormal lymph node medullary cord morphology ( J:45917 )

• increased number of plasma cells in the medullary cords of mesenteric lymph nodes

increased interferon-gamma secretion ( J:134156 )

• there is an increase in the percentage of CD8 T cells producing IFN-gamma compared to wild-type mice

increased interleukin-17 secretion ( J:134156 )

• there is an increased percentage of CD4 T cells producing IL-17 in the mesenteric lymph nodes and the lamina propria of 4-5 week old mice

hematopoietic system

abnormal granulocyte differentiation ( J:45917 )

• increased granulocytopoiesis in sternal bone marrow

extramedullary hematopoiesis ( J:45917 )

• increased in the red pulp of the spleen

• involves erythroid, myeloid, and megakaryocytic lineages

decreased hemoglobin content ( J:45917 )

• decreased peripheral hemoglobin

increased leukocyte cell number ( J:45917 )

• peripheral leukocytosis involving neutrophiles and monocytes

abnormal spleen morphology ( J:45917 )

increased spleen weight ( J:45917 )

• 4 fold increase in the spleen/body weight ratio

spleen hyperplasia ( J:45917 )

• increased numbers of splenocytes

digestive/alimentary system

abnormal crypts of Lieberkuhn morphology ( J:45917 )

• occasional hyperplasia of crypt epithelium

abnormal large intestine morphology ( J:45917 )

• thickened and narrowed

large intestinal inflammation ( J:45917 )

• mixed inflammatory cell mucosal inflammation in the large intestine

• predominantly involves macrophage, neutrophiles and T lymphocytes

colitis ( J:134156 )

• colitis is observed in mice 3-4 months of age with ulcerations found near the iliel-cecal junction, the ascending-to-descending colon transition and the anal-rectal junction

endocrine/exocrine glands

abnormal crypts of Lieberkuhn morphology ( J:45917 )

• occasional hyperplasia of crypt epithelium

cellular

abnormal granulocyte differentiation ( J:45917 )

• increased granulocytopoiesis in sternal bone marrow

growth/size/body

increased spleen weight ( J:45917 )

• 4 fold increase in the spleen/body weight ratio

spleen hyperplasia ( J:45917 )

• increased numbers of splenocytes

Genotype
MGI:3789685

cx2

• Allelic Composition: Il10rb^tm1Agt/Il10rb^tm1Agt; Tg(Cd4-TGFBR2)16Flv/?
• Genetic Background: involves: 129S2/SvPas * C3H * C57BL/6

mortality/aging

premature death ( J:134156 )

• all mice die between 4-6 weeks of age from a fulminate inflammatory bowel disease

growth/size/body

cachexia ( J:134156 )

• mice fail to thrive by 3-4 weeks of age and exhibit rapid weight loss culminating in death between 4-6 weeks of age

immune system

colitis ( J:134156 )

• the cecum and descending colon of mice 4-6 weeks of age exhibit a defuse and marked thickening of the mucusa accompanied by areas of focal ulceration

• there is extensive epithelial hyperplasia, diminished goblet and crypt cell numbers, erosion of surface epithelial cells, numerous crypt abscesses, and mixed leukocytic infiltrates

• there are 10-fold more immune cells found in the lamina propia compared to controls that consists mainly of T cells, NK cells, monocytes, neutrophils and B cells

• colitis can be ameliorated with either combined anti-IFN gamma/ anti-TNF treatment or with broad-spectrum antibiotic treatment

• transferred CD4 T cells from 3 week old mice are able to induce colitis with a similar pathology in immunodeficient recipients

proctitis ( J:134156 )

• inflammation extends into the rectum with significant loss of epithelial crypts and increased width of crypts

• epithelial hyperplasia also occurs as indicated by increased crypt height and elevated M-phase cells per crypt

• an increase in the apoptotic index of rectal epithelial cells and a decrease in epithelial cell height are also observed

abnormal cytokine level ( J:134156 )

increased circulating interferon-gamma level ( J:134156 )

• there is an 18-fold increase in IFN-gamma levels in the sera of 4-5 week old mice

• elevated levels of IFN-gamma are also detected in colon explants from 4-5 week old mice

increased circulating interleukin-6 level ( J:134156 )

• there is a 19-fold increase in IL-6 levels in the sera of 4-5 week old mice

increased circulating tumor necrosis factor level ( J:134156 )

• there is a 6-fold increase in TNF levels in the sera of 4-5 week old mice

abnormal cytokine secretion ( J:134156 )

increased interferon-gamma secretion ( J:134156 )

• there is an increased percentage of CD4 T cells producing IFN-gamma in the mesenteric lymph nodes and the lamina propria of 4-5 week old mice

• there is also an increase in the percentage of CD8 T cells producing IFN-gamma compared to wild-type mice

• elevated levels of IFN-gamma are also detected from colon explants of 4-5 week old mice

increased interleukin-17 secretion ( J:134156 )

• there is an increased percentage of CD4 T cells producing IL-17 in the mesenteric lymph nodes of 4-5 week old mice compared to controls

increased tumor necrosis factor secretion ( J:134156 )

• 32.6% of T cells produce TNF compared to 23.8% of wild-type mice

liver inflammation ( J:134156 )

• small occasional clusters of lymphocytes are located in the portal triads of mice over 4 weeks of age

lung inflammation ( J:134156 )

• small occasional clusters of lymphocytes are located around the bronchi of the lungs

digestive/alimentary system

colitis ( J:134156 )

• the cecum and descending colon of mice 4-6 weeks of age exhibit a defuse and marked thickening of the mucusa accompanied by areas of focal ulceration

• there is extensive epithelial hyperplasia, diminished goblet and crypt cell numbers, erosion of surface epithelial cells, numerous crypt abscesses, and mixed leukocytic infiltrates

• there are 10-fold more immune cells found in the lamina propia compared to controls that consists mainly of T cells, NK cells, monocytes, neutrophils and B cells

• colitis can be ameliorated with either combined anti-IFN gamma/ anti-TNF treatment or with broad-spectrum antibiotic treatment

• transferred CD4 T cells from 3 week old mice are able to induce colitis with a similar pathology in immunodeficient recipients

proctitis ( J:134156 )

• inflammation extends into the rectum with significant loss of epithelial crypts and increased width of crypts

• epithelial hyperplasia also occurs as indicated by increased crypt height and elevated M-phase cells per crypt

• an increase in the apoptotic index of rectal epithelial cells and a decrease in epithelial cell height are also observed

homeostasis/metabolism

abnormal cytokine level ( J:134156 )

increased circulating interferon-gamma level ( J:134156 )

• there is an 18-fold increase in IFN-gamma levels in the sera of 4-5 week old mice

• elevated levels of IFN-gamma are also detected in colon explants from 4-5 week old mice

increased circulating interleukin-6 level ( J:134156 )

• there is a 19-fold increase in IL-6 levels in the sera of 4-5 week old mice

increased circulating tumor necrosis factor level ( J:134156 )

• there is a 6-fold increase in TNF levels in the sera of 4-5 week old mice

liver/biliary system

liver inflammation ( J:134156 )

• small occasional clusters of lymphocytes are located in the portal triads of mice over 4 weeks of age

respiratory system

lung inflammation ( J:134156 )

• small occasional clusters of lymphocytes are located around the bronchi of the lungs

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
inflammatory bowel disease		DOID:0050589	OMIM:PS266600	J:134156