Phenotypes associated with this allele

• Allele Symbol: Tg(Cd4-TGFBR2)16Flv
• Allele Name: transgene insertion 16, Richard A Flavell
• Allele ID: MGI:3575738
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cx1	Il10rb^tm1Agt/Il10rb^tm1Agt Tg(Cd4-TGFBR2)16Flv/?	involves: 129S2/SvPas * C3H * C57BL/6	MGI:3789685
tg2	Tg(Cd4-TGFBR2)16Flv/?	involves: C3H * C57BL/6	MGI:3789684
tg3	Tg(Cd4-TGFBR2)16Flv/?	involves: C3H * C57BL/6 * C57BL/10 * C57BR/cd	MGI:3789638

Genotype
MGI:3789685

cx1

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

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

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

Genotype
MGI:3789684

tg2

• Allelic Composition: Tg(Cd4-TGFBR2)16Flv/?
• Genetic Background: involves: C3H * C57BL/6

digestive/alimentary system

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

immune system

abnormal T cell proliferation ( J:134473 )

• TGF-beta is unable to increase proliferation of in vitro activated CD8 T cells

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

abnormal CD8-positive, alpha-beta regulatory T cell morphology ( J:134473 )

• CD8 T cells fail to express FoxP3 when cultured under conditions that normally generate regulatory CD8 T cells (high costimulation and TGF-beta signaling)

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

increased tumor necrosis factor secretion ( J:134156 )

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

hematopoietic system

abnormal T cell proliferation ( J:134473 )

• TGF-beta is unable to increase proliferation of in vitro activated CD8 T cells

abnormal CD8-positive, alpha-beta regulatory T cell morphology ( J:134473 )

• CD8 T cells fail to express FoxP3 when cultured under conditions that normally generate regulatory CD8 T cells (high costimulation and TGF-beta signaling)

cellular

abnormal T cell proliferation ( J:134473 )

• TGF-beta is unable to increase proliferation of in vitro activated CD8 T cells

Genotype
MGI:3789638

tg3

• Allelic Composition: Tg(Cd4-TGFBR2)16Flv/?
• Genetic Background: involves: C3H * C57BL/6 * C57BL/10 * C57BR/cd

growth/size/body

cachexia ( J:97554 )

• starting about 3 to 4 months of age, mice begin wasting due to an autoimmune disease

spleen hyperplasia ( J:97554 )

• total cell number in the spleen is increased by about 60%

immune system

abnormal thymus involution ( J:97554 )

• thymuses of 5 month old mice are completely involuted with only thymic lymph nodes detectable in the area where the thymus in normally present

spleen hyperplasia ( J:97554 )

• total cell number in the spleen is increased by about 60%

decreased B cell number ( J:97554 )

• there is a decrease in the percentage of B cells found in the spleen though due to the increase in spleen cellularity the total number of B cells is normal

increased memory T cell number ( J:97554 )

• 90% of the T cells found in the spleen of 5 month old mice are CD62L^low CD44^high indicating an activated/memory phenotype

• increases in memory T cell numbers are found as early as 4 weeks of age

increased immunoglobulin level ( J:97554 )

increased IgA level ( J:97554 )

• sera levels of IgA are 16 fold higher in 5-6 month old mice than in age matched wild-type mice

increased IgG1 level ( J:97554 )

• sera levels of IgG1 are 8 fold higher in 5-6 month old mice than in age matched wild-type mice

increased IgG2a level ( J:97554 )

• sera levels of IgG2a are 4 fold higher in 5-6 month old mice than in age matched wild-type mice

abnormal T cell activation ( J:97554 )

• all CD8 T cells and most CD4 T cells are in an activated, effector state with CD8 T cells producing IFN-gamma and CD4 T cells producing Th1 and/or Th2 cytokines

abnormal T cell proliferation ( J:97554 )

• in vitro stimulated CD4- and CD8- T cells are refractory to the inhibitory effects of TGF-beta1 and TGF-beta3 on T cell proliferation

• there is only a slight inhibition of proliferation on activated T cells by TGF-beta2

lymph node hyperplasia ( J:97554 )

• there is a 3-fold increase in the number of cells found in the lymph nodes

increased anti-nuclear antigen antibody level ( J:97554 )

• auto-antibodies to nuclear proteins are detected in the sera of mice with specificity of these antibodies differing between individual mice

increased inflammatory response ( J:97554 )

colitis ( J:97554 )

• pronounced inflammation in the gut is evident in 5 month old mice with dense infiltrates of lymphocytes, macrophages and plasma cells occurring in the lamina propia and mucosal epithelia

• the inflammation also causes distortion of the crypt architecture, crypt abscesses and compensatory epithelial hyperplasia

• mild inflammation is also evident in the stomach and duodenum

pancreas inflammation ( J:97554 )

• mild inflammation is evident in the pancreas of 5 month old mice

liver inflammation ( J:97554 )

• there are clusters of macrophages and lymphocytes located in the parenchyma and adjacent to blood vessels in the liver of 5 month old mice

glomerulonephritis ( J:97554 )

• IgG deposits are found in the kidney glomeruli of 5 month old mice

• mild infiltration of inflammatory cells is also observed

lung inflammation ( J:97554 )

• lungs of 5 month old mice have focal perivascular and intraalveolar infiltration of lymphocytes and macrophages

digestive/alimentary system

diarrhea ( J:97554 )

• mice start developing diarrhea at about 3 to 4 months of age

colitis ( J:97554 )

• pronounced inflammation in the gut is evident in 5 month old mice with dense infiltrates of lymphocytes, macrophages and plasma cells occurring in the lamina propia and mucosal epithelia

• the inflammation also causes distortion of the crypt architecture, crypt abscesses and compensatory epithelial hyperplasia

• mild inflammation is also evident in the stomach and duodenum

endocrine/exocrine glands

abnormal thymus involution ( J:97554 )

• thymuses of 5 month old mice are completely involuted with only thymic lymph nodes detectable in the area where the thymus in normally present

pancreas inflammation ( J:97554 )

• mild inflammation is evident in the pancreas of 5 month old mice

hematopoietic system

abnormal thymus involution ( J:97554 )

• thymuses of 5 month old mice are completely involuted with only thymic lymph nodes detectable in the area where the thymus in normally present

spleen hyperplasia ( J:97554 )

• total cell number in the spleen is increased by about 60%

decreased B cell number ( J:97554 )

• there is a decrease in the percentage of B cells found in the spleen though due to the increase in spleen cellularity the total number of B cells is normal

increased memory T cell number ( J:97554 )

• 90% of the T cells found in the spleen of 5 month old mice are CD62L^low CD44^high indicating an activated/memory phenotype

• increases in memory T cell numbers are found as early as 4 weeks of age

increased immunoglobulin level ( J:97554 )

increased IgA level ( J:97554 )

• sera levels of IgA are 16 fold higher in 5-6 month old mice than in age matched wild-type mice

increased IgG1 level ( J:97554 )

• sera levels of IgG1 are 8 fold higher in 5-6 month old mice than in age matched wild-type mice

increased IgG2a level ( J:97554 )

• sera levels of IgG2a are 4 fold higher in 5-6 month old mice than in age matched wild-type mice

abnormal T cell activation ( J:97554 )

• all CD8 T cells and most CD4 T cells are in an activated, effector state with CD8 T cells producing IFN-gamma and CD4 T cells producing Th1 and/or Th2 cytokines

abnormal T cell proliferation ( J:97554 )

• in vitro stimulated CD4- and CD8- T cells are refractory to the inhibitory effects of TGF-beta1 and TGF-beta3 on T cell proliferation

• there is only a slight inhibition of proliferation on activated T cells by TGF-beta2

liver/biliary system

liver inflammation ( J:97554 )

• there are clusters of macrophages and lymphocytes located in the parenchyma and adjacent to blood vessels in the liver of 5 month old mice

renal/urinary system

glomerulonephritis ( J:97554 )

• IgG deposits are found in the kidney glomeruli of 5 month old mice

• mild infiltration of inflammatory cells is also observed

renal glomerular immunoglobulin deposits ( J:97554 )

respiratory system

lung inflammation ( J:97554 )

• lungs of 5 month old mice have focal perivascular and intraalveolar infiltration of lymphocytes and macrophages

cellular

abnormal T cell proliferation ( J:97554 )

• in vitro stimulated CD4- and CD8- T cells are refractory to the inhibitory effects of TGF-beta1 and TGF-beta3 on T cell proliferation

• there is only a slight inhibition of proliferation on activated T cells by TGF-beta2