Phenotypes associated with this allele

• Allele Symbol: Il2^tm1Hor
• Allele Name: targeted mutation 1, Ivan Horak
• Allele ID: MGI:1857191
• Summary: 19 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Il2^tm1Hor/Il2^tm1Hor	B6.129P2-Il2^tm1Hor	MGI:3759322
hm2	Il2^tm1Hor/Il2^tm1Hor	B6.129P2-Il2^tm1Hor/J	MGI:3760264
hm3	Il2^tm1Hor/Il2^tm1Hor	C.129P2-Il2^tm1Hor	MGI:3759313
hm4	Il2^tm1Hor/Il2^tm1Hor	C3.129P2-Il2^tm1Hor	MGI:3759400
hm5	Il2^tm1Hor/Il2^tm1Hor	involves: 129P2/OlaHsd	MGI:3798944
hm6	Il2^tm1Hor/Il2^tm1Hor	involves: 129P2/OlaHsd * C57BL/6	MGI:2450466
hm7	Il2^tm1Hor/Il2^tm1Hor	involves: 129P2/OlaHsd * C57BL/6J	MGI:4843435
ht8	Il2^tm1Hor/Il2^+	NOD.129P2(B6)-Il2^tm1Hor/DvsJ	MGI:4456211
cx9	Il2^tm1Hor/Il2^tm1Hor Tg(DO11.10)10Dlo/?	C.Cg-Il2^tm1Hor Tg(DO11.10)10Dlo	MGI:3759780
cx10	Il2^tm1Hor/Il2^tm1Hor Tg(Pgk1-HA)1.1Vbo/? Tg(Tcra/Tcrb)1Vbo/?	C.Cg-Il2^tm1Hor Tg(Pgk1-HA)1.1Vbo Tg(Tcra/Tcrb)1Vbo	MGI:3760109
cx11	B2m^tm1Unc/B2m^tm1Unc Il2^tm1Hor/Il2^tm1Hor	involves: 129 * C57BL/6	MGI:3576258
cx12	B2m^tm1Unc/B2m^tm1Unc Il2^tm1Hor/Il2^tm1Hor	involves: 129P2/OlaHsd	MGI:3798945
cx13	Il2^tm1Hor/Il2^tm1Hor Rag2^tm1Fwa/Rag2^+	involves: 129P2/OlaHsd * 129S/SvEv * C57BL/6	MGI:3759417
cx14	Il2^tm1Hor/Il2^tm1Hor Rag2^tm1Fwa/Rag2^tm1Fwa	involves: 129P2/OlaHsd * 129S/SvEv * C57BL/6	MGI:3759416
cx15	Il2^tm1Hor/Il2^tm1Hor Rag2^tm1Fwa/Rag2^tm1Fwa Tg(Tcra5CC7,Tcrb5CC7)IWep/0	involves: 129P2/OlaHsd * C57BL/10	MGI:4843436
cx16	Il2^tm1Hor/Il2^tm1Hor Il4^tm1Cgn/Il4^tm1Cgn	involves: 129P2/OlaHsd * C57BL/6	MGI:3759409
cx17	Il2^tm1Hor/Il2^tm1Hor Tcrb^tm1Mom/Tcrb^tm1Mom	involves: 129P2/OlaHsd * C57BL/6	MGI:4843515
cx18	Igh-J^tm1Dhu/Igh-J^+ Il2^tm1Hor/Il2^tm1Hor	involves: 129/Sv * C57BL/6	MGI:3759414
cx19	Igh-J^tm1Dhu/Igh-J^tm1Dhu Il2^tm1Hor/Il2^tm1Hor	involves: 129/Sv * C57BL/6	MGI:3759413

Genotype
MGI:3759322

hm1

• Allelic Composition: Il2^tm1Hor/Il2^tm1Hor
• Genetic Background: B6.129P2-Il2^tm1Hor

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

immune system

immune system phenotype ( J:125748 )

N • bone marrow chimeras (mutant bone marrow in Rag2-deficient hosts) do not develop a wasting autoimmune disease compared to the lethal disease that develops with Il2ra^tm1Dw bone marrow chimeras

increased T cell proliferation ( J:28924 )

• T cells continue to respond to antigen instead of going into anergy during secondary stimulation with antigens

increased T cell number ( J:125748 )

increased CD4-positive, alpha-beta T cell number ( J:28924 )

• activated T cell numbers fail to decrease to normal levels after immunization with staphylococcal enterotoxin, indicating a problem with peripheral deletion

increased CD8-positive, alpha-beta T cell number ( J:28924 )

• activated T cell numbers decrease with slower kinetics than wild-type mice after after immunization with staphylococcal enterotoxin

increased activated T cell number ( J:28924 )

• higher numbers due to less sensitivity to Fas-mediated cell death (apoptosis)

hematopoietic system

increased T cell proliferation ( J:28924 )

• T cells continue to respond to antigen instead of going into anergy during secondary stimulation with antigens

increased T cell number ( J:125748 )

increased CD4-positive, alpha-beta T cell number ( J:28924 )

• activated T cell numbers fail to decrease to normal levels after immunization with staphylococcal enterotoxin, indicating a problem with peripheral deletion

increased CD8-positive, alpha-beta T cell number ( J:28924 )

• activated T cell numbers decrease with slower kinetics than wild-type mice after after immunization with staphylococcal enterotoxin

increased activated T cell number ( J:28924 )

• higher numbers due to less sensitivity to Fas-mediated cell death (apoptosis)

cellular

increased T cell proliferation ( J:28924 )

• T cells continue to respond to antigen instead of going into anergy during secondary stimulation with antigens

Genotype
MGI:3760264

hm2

• Allelic Composition: Il2^tm1Hor/Il2^tm1Hor
• Genetic Background: B6.129P2-Il2^tm1Hor/J

digestive/alimentary system

abnormal salivary gland morphology ( J:125129 )

• severe acinar gland destruction

abnormal salivary gland duct morphology ( J:125129 )

• mild ductal changes in the salivary gland

large intestinal inflammation ( J:125129 )

• severe inflammation in the colon

• however, mice do show severe inflammation in the lung or the skin

decreased salivation ( J:125129 )

• mice exhibit an increase in the lag time and a reduction of saliva production when treated with Pilocarpine, indicating loss of salivary gland function

salivary gland inflammation ( J:125129 )

• severe inflammation in the salivary glands

• major population of infiltrating leukocytes are lymphocytes and to a much lower extent neutrophils

• salivary glands show presence of a large fraction of T cells and a ratio of CD4+/CD8+ of 1/2

• although more Gr-1+ cells are seen in the salivary glands, the absolute number of neutrophils is relatively small

immune system

large intestinal inflammation ( J:125129 )

• severe inflammation in the colon

• however, mice do show severe inflammation in the lung or the skin

salivary gland inflammation ( J:125129 )

• severe inflammation in the salivary glands

• major population of infiltrating leukocytes are lymphocytes and to a much lower extent neutrophils

• salivary glands show presence of a large fraction of T cells and a ratio of CD4+/CD8+ of 1/2

• although more Gr-1+ cells are seen in the salivary glands, the absolute number of neutrophils is relatively small

lacrimal gland inflammation ( J:125129 )

• severe inflammation in the lacrimal glands

increased CD4-positive, alpha-beta T cell number ( J:131774 )

• 3-fold

decreased regulatory T cell number ( J:113547 )

• there is a 2 to 5 fold reduction in the percentage of CD25-postive CD4 T cells in both the thymus and lymph nodes

decreased CD4-positive, CD25-positive, alpha-beta regulatory T cell number ( J:131774 )

• 4-fold

increased splenocyte number ( J:131774 )

abnormal T cell activation ( J:190168 )

• both CD4+ and CD8+ T cells fail to increase in size and granularity after activation with anti-CD3/28

abnormal T cell proliferation ( J:190168 )

• DNA replication fails to increase in activated CD4+ and CD8+ T cells after activation with anti-CD3/28

abnormal circulating cytokine level ( J:190168 )

decreased circulating interferon-gamma level ( J:190168 )

• after activation with anti-CD3/28

decreased circulating interleukin-13 level ( J:190168 )

• after activation with anti-CD3/28

decreased circulating interleukin-4 level ( J:190168 )

• after activation with anti-CD3/28

enlarged lymph nodes ( J:113547 )

• increased cellularity of lymph nodes compared to wild-type mice, but lower than what is observed in Il2rb^tm1Mak mice

increased susceptibility to autoimmune disorder ( J:113547 )

• generalized symptoms of autoimmunity noted at 4 weeks of age

• transfer of wild-type regulatory T cells did not prevent autoimmune disorder

abnormal response to transplant ( J:113547 )

• wild-type regulatory T cells fail to engraft when adoptively transferred into these mice

endocrine/exocrine glands

abnormal salivary gland morphology ( J:125129 )

• severe acinar gland destruction

abnormal salivary gland duct morphology ( J:125129 )

• mild ductal changes in the salivary gland

decreased salivation ( J:125129 )

• mice exhibit an increase in the lag time and a reduction of saliva production when treated with Pilocarpine, indicating loss of salivary gland function

salivary gland inflammation ( J:125129 )

• severe inflammation in the salivary glands

• major population of infiltrating leukocytes are lymphocytes and to a much lower extent neutrophils

• salivary glands show presence of a large fraction of T cells and a ratio of CD4+/CD8+ of 1/2

• although more Gr-1+ cells are seen in the salivary glands, the absolute number of neutrophils is relatively small

lacrimal gland inflammation ( J:125129 )

• severe inflammation in the lacrimal glands

cellular

abnormal T cell proliferation ( J:190168 )

• DNA replication fails to increase in activated CD4+ and CD8+ T cells after activation with anti-CD3/28

abnormal cellular respiration ( J:190168 )

• fail to switch from oxidative phosphorylation to aerobic glycolysis after 5 days of tamoxifen treatment and activation with anti-CD3/28

vision/eye

lacrimal gland inflammation ( J:125129 )

• severe inflammation in the lacrimal glands

homeostasis/metabolism

decreased salivation ( J:125129 )

• mice exhibit an increase in the lag time and a reduction of saliva production when treated with Pilocarpine, indicating loss of salivary gland function

abnormal circulating cytokine level ( J:190168 )

decreased circulating interferon-gamma level ( J:190168 )

• after activation with anti-CD3/28

decreased circulating interleukin-13 level ( J:190168 )

• after activation with anti-CD3/28

decreased circulating interleukin-4 level ( J:190168 )

• after activation with anti-CD3/28

hematopoietic system

increased CD4-positive, alpha-beta T cell number ( J:131774 )

• 3-fold

decreased regulatory T cell number ( J:113547 )

• there is a 2 to 5 fold reduction in the percentage of CD25-postive CD4 T cells in both the thymus and lymph nodes

decreased CD4-positive, CD25-positive, alpha-beta regulatory T cell number ( J:131774 )

• 4-fold

increased splenocyte number ( J:131774 )

abnormal T cell activation ( J:190168 )

• both CD4+ and CD8+ T cells fail to increase in size and granularity after activation with anti-CD3/28

abnormal T cell proliferation ( J:190168 )

• DNA replication fails to increase in activated CD4+ and CD8+ T cells after activation with anti-CD3/28

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Sjogren's syndrome		DOID:12894	OMIM:270150	J:125129

Genotype
MGI:3759313

hm3

• Allelic Composition: Il2^tm1Hor/Il2^tm1Hor
• Genetic Background: C.129P2-Il2^tm1Hor

mortality/aging

premature death ( J:29799 )

• Background Sensitivity: mice all die by 5 weeks of age, compared to death by 25 weeks of age for mice homozygous for the same mutant locus on a B6.129P2 background

immune system

increased B cell proliferation ( J:29799 )

• faster proliferation as measured by BrdU incorporation

increased T cell proliferation ( J:29799 )

• by 10 days of age, T cells in lymph nodes express high levels of activation markers and are proliferating at an increased rate

• CD4 T cells are activated prior to CD8 T cells (10 days vs. 15 days of age)

increased susceptibility to autoimmune hemolytic anemia ( J:29799 )

• Background Sensitivity: cause of death for mice on this genetic background, as opposed to death caused by inflammatory bowel disease for homozygous mice on a B6.129P2 genetic background

abnormal lymphocyte morphology ( J:29799 )

increased germinal center B cell number ( J:29799 )

increased plasma cell number ( J:29799 )

• seen in the spleen by 15 days of age

abnormal spleen morphology ( J:29799 )

spleen hyperplasia ( J:29799 )

• 15 day old mice exhibit hyperplasia of the white pulp

increased spleen red pulp amount ( J:29799 )

increased IgG level ( J:29799 )

• increased level of IgG secreting B cells from spleen and lymph nodes

abnormal regulatory T cell physiology ( J:112603 )

• there is a rapid loss of adoptively transferred regulatory T cells

enlarged lymph nodes ( J:29799 )

increased inflammatory response ( J:29799 )

heart inflammation ( J:29799 )

• moderate to severe inflammation noted upon necropsy

pancreas inflammation ( J:29799 )

• moderate to severe inflammation noted upon necropsy

liver inflammation ( J:29799 )

lung inflammation ( J:29799 )

• moderate to severe inflammation noted upon necropsy

hematopoietic system

increased B cell proliferation ( J:29799 )

• faster proliferation as measured by BrdU incorporation

increased T cell proliferation ( J:29799 )

• by 10 days of age, T cells in lymph nodes express high levels of activation markers and are proliferating at an increased rate

• CD4 T cells are activated prior to CD8 T cells (10 days vs. 15 days of age)

increased susceptibility to autoimmune hemolytic anemia ( J:29799 )

• Background Sensitivity: cause of death for mice on this genetic background, as opposed to death caused by inflammatory bowel disease for homozygous mice on a B6.129P2 genetic background

abnormal bone marrow cell number ( J:29799 )

• invasion of T cells occur, with a concurrent drop in B cells and other nucleated cells

low mean erythrocyte cell number ( J:29799 )

decreased hematocrit ( J:29799 )

increased mean corpuscular hemoglobin ( J:29799 )

• about twice normal levels, this indicates a hyperchromic anemia

abnormal lymphocyte morphology ( J:29799 )

increased germinal center B cell number ( J:29799 )

increased plasma cell number ( J:29799 )

• seen in the spleen by 15 days of age

abnormal reticulocyte morphology ( J:29799 )

• marked reduction concurrent with T cell invasion of marrow

abnormal spleen morphology ( J:29799 )

spleen hyperplasia ( J:29799 )

• 15 day old mice exhibit hyperplasia of the white pulp

increased spleen red pulp amount ( J:29799 )

increased IgG level ( J:29799 )

• increased level of IgG secreting B cells from spleen and lymph nodes

abnormal regulatory T cell physiology ( J:112603 )

• there is a rapid loss of adoptively transferred regulatory T cells

homeostasis/metabolism

increased circulating bilirubin level ( J:29799 )

cardiovascular system

vascular inflammation ( J:29799 )

• moderate to severe inflammation noted in the major thoracic blood vessels upon necropsy

heart inflammation ( J:29799 )

• moderate to severe inflammation noted upon necropsy

endocrine/exocrine glands

pancreas inflammation ( J:29799 )

• moderate to severe inflammation noted upon necropsy

liver/biliary system

liver inflammation ( J:29799 )

respiratory system

lung inflammation ( J:29799 )

• moderate to severe inflammation noted upon necropsy

cellular

increased B cell proliferation ( J:29799 )

• faster proliferation as measured by BrdU incorporation

increased T cell proliferation ( J:29799 )

• by 10 days of age, T cells in lymph nodes express high levels of activation markers and are proliferating at an increased rate

• CD4 T cells are activated prior to CD8 T cells (10 days vs. 15 days of age)

growth/size/body

spleen hyperplasia ( J:29799 )

• 15 day old mice exhibit hyperplasia of the white pulp

Genotype
MGI:3759400

hm4

• Allelic Composition: Il2^tm1Hor/Il2^tm1Hor
• Genetic Background: C3.129P2-Il2^tm1Hor

hematopoietic system

increased CD4-positive, alpha-beta T cell number ( J:28924 )

• activated T cell numbers fail to decrease to normal levels after immunization with staphylococcal enterotoxin, indicating a problem with peripheral deletion

increased CD8-positive, alpha-beta T cell number ( J:28924 )

• activated T cell numbers decrease with slower kinetics than wild-type mice after after immunization with staphylococcal enterotoxin

immune system

increased CD4-positive, alpha-beta T cell number ( J:28924 )

• activated T cell numbers fail to decrease to normal levels after immunization with staphylococcal enterotoxin, indicating a problem with peripheral deletion

increased CD8-positive, alpha-beta T cell number ( J:28924 )

• activated T cell numbers decrease with slower kinetics than wild-type mice after after immunization with staphylococcal enterotoxin

Genotype
MGI:3798944

hm5

• Allelic Composition: Il2^tm1Hor/Il2^tm1Hor
• Genetic Background: involves: 129P2/OlaHsd

reproductive system

reproductive system phenotype ( J:134589 )

N • there are no abnormalities of the placenta, the mesometrial triangle, and differentiation of granulated metrial gland cells (aka uterine NK cells) in the uteri of pregnant mice at day 14 of gestation

immune system

increased regulatory T cell number ( J:208318 )

• of CD25^lo regulatory T cells

hematopoietic system

increased regulatory T cell number ( J:208318 )

• of CD25^lo regulatory T cells

Genotype
MGI:2450466

hm6

• Allelic Composition: Il2^tm1Hor/Il2^tm1Hor
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

mortality/aging

premature death ( J:15223 )

• about of 50% of mice die within the first 9 weeks of age with enlarged lymphoid organs and severe anemia

• the remaining mice die by 25 weeks of age from inflammatory bowel disease

digestive/alimentary system

rectal hemorrhage ( J:29999 )

• rarely observed

abnormal colon goblet cell morphology ( J:15223 , J:29999 )

• colon epithelium shows loss of goblet cells (J:15223)

• loss of mucin is observed in goblet cells (J:29999)

diarrhea ( J:29999 )

• occurs in mice 24 weeks of age

chronic diarrhea ( J:15223 )

• all mice that do not die within the first 9 weeks after birth exhibit diarrhea

abnormal intestinal epithelium morphology ( J:15223 , J:29999 )

• prominent epithelial regeneration with crypt branching and dysplasia near areas of inflammation (J:15223)

• crypt hyperplasia and unusual branching is observed (J:29999)

crypts of Lieberkuhn abscesses ( J:15223 )

• frequently occurres in the large intestine

intestinal ulcer ( J:15223 )

• ulcers occur in the large intestine, with pronounced thickening of the bowel wall

rectal prolapse ( J:15223 , J:29999 )

• frequent occurrence among mice whom live past 9 weeks of age (J:15223)

• occasional occurrence among mice whom live past 9 weeks of age (J:29999)

colitis ( J:15223 , J:29999 , J:37220 )

• all mice that do not die within the first 9 weeks after birth develop an inflammatory bowel disease that is similar to the human disease ulcerative colitis (J:15223)

• infiltrating lymphocytes sometimes form nodules (J:15223)

• mice bred in a germ-free facility do not display any histopathological signs of colitis (J:15223)

• mice bred under specific pathogen free conditions do not develop any clinical signs of colitis but histological and immunological examinations show the beginning of inflammatory processes in mice that are 17-20 weeks of age (J:15223)

• occurs in all mice that survive past 9 weeks of age, with thickening of large intestinal wall (J:29999)

• mice kept under a specific pathogen free environment develop colitis when immunized with an antigen that activates CD4 T cells (J:37220)

immune system

decreased splenocyte proliferation ( J:79241 )

• proliferative response of splenocytes to anti-CD3 antibody is only 16% of wt controls

• poor proliferative response to anti-CD3 antibody is partially rescued by addition of cytokines including IL-2, IL-4, IL-7

• there is reduced proliferation to allogenic leukocytes

colitis ( J:15223 , J:29999 , J:37220 )

• all mice that do not die within the first 9 weeks after birth develop an inflammatory bowel disease that is similar to the human disease ulcerative colitis (J:15223)

• infiltrating lymphocytes sometimes form nodules (J:15223)

• mice bred in a germ-free facility do not display any histopathological signs of colitis (J:15223)

• mice bred under specific pathogen free conditions do not develop any clinical signs of colitis but histological and immunological examinations show the beginning of inflammatory processes in mice that are 17-20 weeks of age (J:15223)

• occurs in all mice that survive past 9 weeks of age, with thickening of large intestinal wall (J:29999)

• mice kept under a specific pathogen free environment develop colitis when immunized with an antigen that activates CD4 T cells (J:37220)

enlarged spleen ( J:15223 )

• occurs in the 50% of mice that die prematurely

abnormal lymphocyte morphology ( J:37220 )

• decreased apoptosis in thymus upon injection with anti-CD3 antibody

increased pro-B cell number ( J:16662 )

• of cells in the bone marrow

abnormal T-helper 1 cell differentiation ( J:37220 )

• 10 fold greater amounts of IFN gamma were made by thymocytes from immunized mutant mice as measured by an in vitro assay

• low levels of the Th2 cytokine IL-4 were made compared to the large level made by wt thymocytes

• however, treatment with an IL-12 neutralizing antibody normalized Th1cytokine levels

abnormal lymphocyte cell number ( J:15223 )

decreased double-negative T cell number ( J:15223 )

• there is a drastic reduction in the colon

increased double-negative T cell number ( J:37220 )

• percentage of these cells is increased (11.2% vs 3.7%) in the thymus when mice are immunized with a CD4 T cell activating antigen

decreased double-positive T cell number ( J:37220 )

• percentage of these cells is decreased (47.0% vs 86.2%) in the thymus when mice are immunized with a CD4 T cell activating antigen

increased pre-B cell number ( J:16662 )

• of cells in the bone marrow

increased single-positive T cell number ( J:37220 )

• percentage of these cells is increased (41.8% vs 20.9.2%) in the thymus when mice are immunized with a CD4 T cell activating antigen

• however, treatment with an IL-12 neutralizing antibody normalized SP cell numbers

abnormal CD8 positive, alpha-beta intraepithelial T cell morphology ( J:15223 , J:39981 )

• increased number (5-100 fold) are found in diseased colon (J:15223)

• T cells expressing the CD8 alpha-beta heterodimer predominate over CD8 alpha-alpha T cells (J:39981)

abnormal gamma-delta intraepithelial T cell morphology ( J:15223 )

• decreased percentage of these cells are found in the colon epithelium

abnormal lymphocyte physiology ( J:15223 )

increased B cell proliferation ( J:16662 )

• B cells from lymph nodes have a larger size and incorporate more BrdU, indicating a faster proliferation rate

decreased T cell proliferation ( J:26198 , J:39989 )

increased T cell proliferation ( J:15223 , J:16662 )

• the proliferation of T cells in the colon is twice that of wild-type controls (J:15223)

• 2-10 fold higher using in vivo incorporation of BrdU, which indicates a faster proliferation rate (J:16662)

abnormal thymocyte activation ( J:37220 , J:39989 )

• increased activation of thymocytes 7 days after immunization with a CD4 T cell activating antigen, as measured by expression of CD69 and Icam1 (J:37220)

• however, treatment with an IL-12 neutralizing antibody normalized the percentage of activated thymocytes (J:37220)

• in vitro proliferation is reduced in presence of concanavalin A or anti-CD3 antibody (J:39989)

abnormal class switch recombination ( J:15573 )

• there is delayed class switching from IgM to IgG after infection with vesicular stomatitis virus

increased IgA level ( J:15223 )

• drastic elevation in secretion by B cells found in the colon

increased IgE level ( J:16662 )

• levels are 10 fold higher than those observed in wild-type mice

increased IgG1 level ( J:15223 , J:16662 , J:39989 )

• drastic elevation in secretion of IgG1 by B cells found in the colon (J:15223)

• levels of IgG1 are increased 100 fold (J:16662)

• levels of IgG1 are drastically increased to levels above 2700 ug/ml (J:39989)

increased IgG2a level ( J:16662 )

• levels of IgG2a are also elevated

increased IgG2b level ( J:16662 )

• levels of IgG2b are also elevated

impaired natural killer cell mediated cytotoxicity ( J:15573 )

• 3 to 9 fold reduction in killing of NK susceptible target cells as measured by chromium release assay

abnormal CD4-positive, alpha-beta T cell physiology ( J:15573 , J:39981 , J:39989 )

• there is an impaired ability to induce Ig class switching in B cells after infection with vesicular stomatitis virus (J:15573)

• increased cytotoxic effectiveness of CD4 T cells isolated from the colon (J:39981)

• unable to induce IgM secretion from activated B cells in an in vitro assay (J:39989)

• however, IgM levels are in vivo are normal (J:39989)

abnormal cytotoxic T cell physiology ( J:39981 )

• enhanced target cell killing by intraepithelial lymphocytes T cells (IEL) and lamina propia lymphocytes of the large intestine

• enhanced target cell killing by intraepithelial lymphocytes T cells (IEL) of the small intestine

decreased cytotoxic T cell cytolysis ( J:15573 , J:26198 , J:26861 )

• there is a three fold reduction of target cell killing by primary T cells in a chromium release assay (J:15573)

• no target cell killing by previously stimulated T cells in a chromium release assay (J:15573)

• there is reduced killing of allogeneic tumor cells in an in vitro assay (J:26198)

• footpad swelling is reduced 6-10 days after infection with lymphocytic choriomeningitis virus (J:26861)

enlarged mesenteric lymph nodes ( J:29999 )

• increased 3-10 fold in size as compared to control littermates

enlarged lymph nodes ( J:15223 )

lymph node hyperplasia ( J:16662 )

abnormal level of surface class II molecules ( J:15223 )

• expression occurs in high number of colon epithelial cells

abnormal susceptibility to Riboviria infection ( J:26861 )

• despite reduced cytotoxic T cell activity, mice still clear lymphocytic choriomeningitis virus within nine days of infection

increased length of allograft survival ( J:26198 )

• graft rejection of allogeneic pancreatic islet cells is delayed by 11 days compared to controls

growth/size/body

cachexia ( J:29999 )

• weight loss resulting from intestinal inflammation is observed by 24 weeks

enlarged spleen ( J:15223 )

• occurs in the 50% of mice that die prematurely

hematopoietic system

decreased splenocyte proliferation ( J:79241 )

• proliferative response of splenocytes to anti-CD3 antibody is only 16% of wt controls

• poor proliferative response to anti-CD3 antibody is partially rescued by addition of cytokines including IL-2, IL-4, IL-7

• there is reduced proliferation to allogenic leukocytes

enlarged spleen ( J:15223 )

• occurs in the 50% of mice that die prematurely

anemia ( J:15223 , J:29999 )

• severe anemia is found in 50% of mice that die prematurely (J:15223)

• occurs in mice 24 weeks of age (J:29999)

abnormal lymphocyte morphology ( J:37220 )

• decreased apoptosis in thymus upon injection with anti-CD3 antibody

increased pro-B cell number ( J:16662 )

• of cells in the bone marrow

abnormal T-helper 1 cell differentiation ( J:37220 )

• 10 fold greater amounts of IFN gamma were made by thymocytes from immunized mutant mice as measured by an in vitro assay

• low levels of the Th2 cytokine IL-4 were made compared to the large level made by wt thymocytes

• however, treatment with an IL-12 neutralizing antibody normalized Th1cytokine levels

abnormal lymphocyte cell number ( J:15223 )

decreased double-negative T cell number ( J:15223 )

• there is a drastic reduction in the colon

increased double-negative T cell number ( J:37220 )

• percentage of these cells is increased (11.2% vs 3.7%) in the thymus when mice are immunized with a CD4 T cell activating antigen

decreased double-positive T cell number ( J:37220 )

• percentage of these cells is decreased (47.0% vs 86.2%) in the thymus when mice are immunized with a CD4 T cell activating antigen

increased pre-B cell number ( J:16662 )

• of cells in the bone marrow

increased single-positive T cell number ( J:37220 )

• percentage of these cells is increased (41.8% vs 20.9.2%) in the thymus when mice are immunized with a CD4 T cell activating antigen

• however, treatment with an IL-12 neutralizing antibody normalized SP cell numbers

abnormal CD8 positive, alpha-beta intraepithelial T cell morphology ( J:15223 , J:39981 )

• increased number (5-100 fold) are found in diseased colon (J:15223)

• T cells expressing the CD8 alpha-beta heterodimer predominate over CD8 alpha-alpha T cells (J:39981)

abnormal gamma-delta intraepithelial T cell morphology ( J:15223 )

• decreased percentage of these cells are found in the colon epithelium

abnormal lymphocyte physiology ( J:15223 )

increased B cell proliferation ( J:16662 )

• B cells from lymph nodes have a larger size and incorporate more BrdU, indicating a faster proliferation rate

decreased T cell proliferation ( J:26198 , J:39989 )

increased T cell proliferation ( J:15223 , J:16662 )

• the proliferation of T cells in the colon is twice that of wild-type controls (J:15223)

• 2-10 fold higher using in vivo incorporation of BrdU, which indicates a faster proliferation rate (J:16662)

abnormal thymocyte activation ( J:37220 , J:39989 )

• increased activation of thymocytes 7 days after immunization with a CD4 T cell activating antigen, as measured by expression of CD69 and Icam1 (J:37220)

• however, treatment with an IL-12 neutralizing antibody normalized the percentage of activated thymocytes (J:37220)

• in vitro proliferation is reduced in presence of concanavalin A or anti-CD3 antibody (J:39989)

abnormal class switch recombination ( J:15573 )

• there is delayed class switching from IgM to IgG after infection with vesicular stomatitis virus

increased IgA level ( J:15223 )

• drastic elevation in secretion by B cells found in the colon

increased IgE level ( J:16662 )

• levels are 10 fold higher than those observed in wild-type mice

increased IgG1 level ( J:15223 , J:16662 , J:39989 )

• drastic elevation in secretion of IgG1 by B cells found in the colon (J:15223)

• levels of IgG1 are increased 100 fold (J:16662)

• levels of IgG1 are drastically increased to levels above 2700 ug/ml (J:39989)

increased IgG2a level ( J:16662 )

• levels of IgG2a are also elevated

increased IgG2b level ( J:16662 )

• levels of IgG2b are also elevated

impaired natural killer cell mediated cytotoxicity ( J:15573 )

• 3 to 9 fold reduction in killing of NK susceptible target cells as measured by chromium release assay

abnormal CD4-positive, alpha-beta T cell physiology ( J:15573 , J:39981 , J:39989 )

• there is an impaired ability to induce Ig class switching in B cells after infection with vesicular stomatitis virus (J:15573)

• increased cytotoxic effectiveness of CD4 T cells isolated from the colon (J:39981)

• unable to induce IgM secretion from activated B cells in an in vitro assay (J:39989)

• however, IgM levels are in vivo are normal (J:39989)

abnormal cytotoxic T cell physiology ( J:39981 )

• enhanced target cell killing by intraepithelial lymphocytes T cells (IEL) and lamina propia lymphocytes of the large intestine

• enhanced target cell killing by intraepithelial lymphocytes T cells (IEL) of the small intestine

decreased cytotoxic T cell cytolysis ( J:15573 , J:26198 , J:26861 )

• there is a three fold reduction of target cell killing by primary T cells in a chromium release assay (J:15573)

• no target cell killing by previously stimulated T cells in a chromium release assay (J:15573)

• there is reduced killing of allogeneic tumor cells in an in vitro assay (J:26198)

• footpad swelling is reduced 6-10 days after infection with lymphocytic choriomeningitis virus (J:26861)

endocrine/exocrine glands

abnormal colon goblet cell morphology ( J:15223 , J:29999 )

• colon epithelium shows loss of goblet cells (J:15223)

• loss of mucin is observed in goblet cells (J:29999)

crypts of Lieberkuhn abscesses ( J:15223 )

• frequently occurres in the large intestine

abnormal thymocyte activation ( J:37220 , J:39989 )

• increased activation of thymocytes 7 days after immunization with a CD4 T cell activating antigen, as measured by expression of CD69 and Icam1 (J:37220)

• however, treatment with an IL-12 neutralizing antibody normalized the percentage of activated thymocytes (J:37220)

• in vitro proliferation is reduced in presence of concanavalin A or anti-CD3 antibody (J:39989)

behavior/neurological

hunched posture ( J:29999 )

• occurs in mice 24 weeks of age

cardiovascular system

rectal hemorrhage ( J:29999 )

• rarely observed

homeostasis/metabolism

amyloidosis ( J:15223 )

• predominately in liver, spleen, and kidneys

cellular

abnormal colon goblet cell morphology ( J:15223 , J:29999 )

• colon epithelium shows loss of goblet cells (J:15223)

• loss of mucin is observed in goblet cells (J:29999)

increased B cell proliferation ( J:16662 )

• B cells from lymph nodes have a larger size and incorporate more BrdU, indicating a faster proliferation rate

decreased T cell proliferation ( J:26198 , J:39989 )

increased T cell proliferation ( J:15223 , J:16662 )

• the proliferation of T cells in the colon is twice that of wild-type controls (J:15223)

• 2-10 fold higher using in vivo incorporation of BrdU, which indicates a faster proliferation rate (J:16662)

decreased splenocyte proliferation ( J:79241 )

• proliferative response of splenocytes to anti-CD3 antibody is only 16% of wt controls

• poor proliferative response to anti-CD3 antibody is partially rescued by addition of cytokines including IL-2, IL-4, IL-7

• there is reduced proliferation to allogenic leukocytes

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
inflammatory bowel disease		DOID:0050589	OMIM:PS266600	J:15223

Genotype
MGI:4843435

hm7

• Allelic Composition: Il2^tm1Hor/Il2^tm1Hor
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6J

immune system

increased T-helper 17 cell number ( J:120176 )

• increase in the percentage of IL-17-producing cells in culturing CD4+ T cells in vitro under Th17-polarizing conditions

• greater proportion of IL-17-positive cells (most of which CD4 positive) in peripheral lymph nodes

• 30-fold difference in absolute numbers of mesenteric Th17 cells compared with wild-type mice

increased circulating interleukin-17 level ( J:120176 )

• elevated serum IL-17 concentration at 3 months old

homeostasis/metabolism

increased circulating interleukin-17 level ( J:120176 )

• elevated serum IL-17 concentration at 3 months old

hematopoietic system

increased T-helper 17 cell number ( J:120176 )

• increase in the percentage of IL-17-producing cells in culturing CD4+ T cells in vitro under Th17-polarizing conditions

• greater proportion of IL-17-positive cells (most of which CD4 positive) in peripheral lymph nodes

• 30-fold difference in absolute numbers of mesenteric Th17 cells compared with wild-type mice

Genotype
MGI:4456211

ht8

• Allelic Composition: Il2^tm1Hor/Il2⁺
• Genetic Background: NOD.129P2(B6)-Il2^tm1Hor/DvsJ

immune system

increased susceptibility to autoimmune diabetes ( J:120349 )

• heterozygotes have an accelerated onset of diabetes and resultant shorter average lifespan than do NOD controls

Genotype
MGI:3759780

cx9

• Allelic Composition: Il2^tm1Hor/Il2^tm1Hor; Tg(DO11.10)10Dlo/?
• Genetic Background: C.Cg-Il2^tm1Hor Tg(DO11.10)10Dlo

mortality/aging

premature death ( J:88349 )

• the mean survival time is 4 months, which is significantly shorter than the average life expectancy of BALB/C mic

• however, the mean survival time is much longer than Il2 null mice on a BALB/c background that do not carry the TCR transgene

immune system

increased T cell proliferation ( J:88349 )

• when transferred into athymic mice, CD4 T cells continue to proliferate for up to three weeks in response to antigen

• CD 4 T cells from these transfer experiments also express high levels of activation markers

• However, when transferred with wild-type CD4-postive CD25-positive T cells, the mutant CD4 T cells stop proliferating between one to two weeks after antigen encounter

increased activated T cell number ( J:88349 )

• when transferred into athymic mice, there are 10-100 fold higher numbers of activated T cells three weeks after antigen

abnormal regulatory T cell physiology ( J:88349 )

• the abnormal proliferation of CD4 T cells upon transfer into athymic mice is reduced by the addition of wild-type CD4-postive CD25-positive T cells

• this suggests there is a defect in the regulatory T cell population in these mice

hematopoietic system

increased T cell proliferation ( J:88349 )

• when transferred into athymic mice, CD4 T cells continue to proliferate for up to three weeks in response to antigen

• CD 4 T cells from these transfer experiments also express high levels of activation markers

• However, when transferred with wild-type CD4-postive CD25-positive T cells, the mutant CD4 T cells stop proliferating between one to two weeks after antigen encounter

increased activated T cell number ( J:88349 )

• when transferred into athymic mice, there are 10-100 fold higher numbers of activated T cells three weeks after antigen

abnormal regulatory T cell physiology ( J:88349 )

• the abnormal proliferation of CD4 T cells upon transfer into athymic mice is reduced by the addition of wild-type CD4-postive CD25-positive T cells

• this suggests there is a defect in the regulatory T cell population in these mice

cellular

increased T cell proliferation ( J:88349 )

• when transferred into athymic mice, CD4 T cells continue to proliferate for up to three weeks in response to antigen

• CD 4 T cells from these transfer experiments also express high levels of activation markers

• However, when transferred with wild-type CD4-postive CD25-positive T cells, the mutant CD4 T cells stop proliferating between one to two weeks after antigen encounter

Genotype
MGI:3760109

cx10

• Allelic Composition: Il2^tm1Hor/Il2^tm1Hor; Tg(Pgk1-HA)1.1Vbo/?; Tg(Tcra/Tcrb)1Vbo/?
• Genetic Background: C.Cg-Il2^tm1Hor Tg(Pgk1-HA)1.1Vbo Tg(Tcra/Tcrb)1Vbo

hematopoietic system

decreased regulatory T cell number ( J:112603 )

• CD25-positive CD4 T cells were almost completely absent in the lymph nodes and spleen, indicating that IL2 is needed to maintain this regulatory T subset

increased regulatory T cell number ( J:112603 )

• in the thymus, there is a substantial increase in the frequency and absolute numbers of CD25-positive CD4 T cells that have the characteristics of regulatory T cells

• this phenotype is similar to mice that express the same transgenes but have the Il2 locus intact, indicating that IL2 is not needed to generate this regulatory T cell subset

abnormal regulatory T cell physiology ( J:112603 )

• in the thymus, CD25-positive CD4 T cells express high levels of Foxp3

• this phenotype in the thymus is similar to transgenic mice that have the Il2 locus intact, indicating that IL2 is not needed to generate this regulatory T cell subset

• only 0.5% of CD25-positive CD4 T cells in the lymph nodes and spleen express Foxp3 compared to 9% of these cells in transgenic mice with the Il2 locus intact

immune system

decreased regulatory T cell number ( J:112603 )

• CD25-positive CD4 T cells were almost completely absent in the lymph nodes and spleen, indicating that IL2 is needed to maintain this regulatory T subset

increased regulatory T cell number ( J:112603 )

• in the thymus, there is a substantial increase in the frequency and absolute numbers of CD25-positive CD4 T cells that have the characteristics of regulatory T cells

• this phenotype is similar to mice that express the same transgenes but have the Il2 locus intact, indicating that IL2 is not needed to generate this regulatory T cell subset

abnormal regulatory T cell physiology ( J:112603 )

• in the thymus, CD25-positive CD4 T cells express high levels of Foxp3

• this phenotype in the thymus is similar to transgenic mice that have the Il2 locus intact, indicating that IL2 is not needed to generate this regulatory T cell subset

• only 0.5% of CD25-positive CD4 T cells in the lymph nodes and spleen express Foxp3 compared to 9% of these cells in transgenic mice with the Il2 locus intact

Genotype
MGI:3576258

cx11

• Allelic Composition: B2m^tm1Unc/B2m^tm1Unc; Il2^tm1Hor/Il2^tm1Hor
• Genetic Background: involves: 129 * C57BL/6

immune system

colitis ( J:39981 , J:51450 )

• colitis progresses faster in these mice compared to mice with targeted mutations of just the Il2 gene (J:39981)

• 75% have colitis at 6-12 months of age (J:51450)

abnormal CD4-positive T cell differentiation ( J:39981 )

• T cells isolated from lymph nodes and the colon have markers indicating an activated or memory-like phenotype

abnormal CD8-positive, alpha beta T cell morphology ( J:51450 )

• mesenteric lymph nodes do not contain CD8+ T cells

abnormal CD8 positive, alpha-beta intraepithelial T cell morphology ( J:39981 )

• <1% of CD8 T cells found in the intestinal mucosa

abnormal CD8-positive, alpha-beta cytotoxic T cell morphology ( J:39981 )

• <1% of CD8 T cells found

abnormal CD4-positive, alpha-beta T cell physiology ( J:51450 )

• chronically activated CD4+ T cells in the mesenteric lymph node and lamina propria lymphocyte compartments

• increased IFN-gamma production by CD4+ T cells in the mesenteric lymph node and lamina propria lymphocyte compartments of colitic double mutants

digestive/alimentary system

diarrhea ( J:39981 , J:51450 )

• 70% of mice exhibit this by 15 weeks of age, compared to 25% of mice to mice with targeted mutations of just the Il2 gene (J:39981)

rectal prolapse ( J:51450 )

• several mutants develop rectal prolapse

increased intestinal adenocarcinoma incidence ( J:51450 )

• 29% incidence of adenocarcinomas in the proximal half of the colon

• most mutants with tumors were between 6-8 months old and no tumors seen at 6 months or younger

• tumors are well to moderately differentiated, invading into or through the muscularis propria with a surrounding desmoplastic stromal response

colitis ( J:39981 , J:51450 )

• colitis progresses faster in these mice compared to mice with targeted mutations of just the Il2 gene (J:39981)

• 75% have colitis at 6-12 months of age (J:51450)

neoplasm

increased intestinal adenocarcinoma incidence ( J:51450 )

• 29% incidence of adenocarcinomas in the proximal half of the colon

• most mutants with tumors were between 6-8 months old and no tumors seen at 6 months or younger

• tumors are well to moderately differentiated, invading into or through the muscularis propria with a surrounding desmoplastic stromal response

growth/size/body

cachexia ( J:39981 , J:51450 )

• 70% of mice exhibit this by 15 weeks of age, compared to 25% of homozygote mice with targeted mutations of just the Il2 gene (J:39981)

hematopoietic system

abnormal CD4-positive T cell differentiation ( J:39981 )

• T cells isolated from lymph nodes and the colon have markers indicating an activated or memory-like phenotype

abnormal CD8-positive, alpha beta T cell morphology ( J:51450 )

• mesenteric lymph nodes do not contain CD8+ T cells

abnormal CD8 positive, alpha-beta intraepithelial T cell morphology ( J:39981 )

• <1% of CD8 T cells found in the intestinal mucosa

abnormal CD8-positive, alpha-beta cytotoxic T cell morphology ( J:39981 )

• <1% of CD8 T cells found

abnormal CD4-positive, alpha-beta T cell physiology ( J:51450 )

• chronically activated CD4+ T cells in the mesenteric lymph node and lamina propria lymphocyte compartments

• increased IFN-gamma production by CD4+ T cells in the mesenteric lymph node and lamina propria lymphocyte compartments of colitic double mutants

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
inflammatory bowel disease		DOID:0050589	OMIM:PS266600	J:51450

Genotype
MGI:3798945

cx12

• Allelic Composition: B2m^tm1Unc/B2m^tm1Unc; Il2^tm1Hor/Il2^tm1Hor
• Genetic Background: involves: 129P2/OlaHsd

reproductive system

reproductive system phenotype ( J:134589 )

N • there are no abnormalities of the placenta, the mesometrial triangle, and differentiation of granulated metrial gland cells (aka uterine NK cells) in the uteri of pregnant mice at day 14 of gestation

Genotype
MGI:3759417

cx13

• Allelic Composition: Il2^tm1Hor/Il2^tm1Hor; Rag2^tm1Fwa/Rag2⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S/SvEv * C57BL/6

immune system

colitis ( J:29999 )

• occurs in all mice that survive past 9 weeks of age, with thickening of large intestinal wall

enlarged mesenteric lymph nodes ( J:29999 )

• are increased 3-10 fold in size as compared to control littermates

digestive/alimentary system

rectal hemorrhage ( J:29999 )

• is rarely observed

abnormal intestinal goblet cell morphology ( J:29999 )

• loss of mucin is observed in goblet cells

diarrhea ( J:29999 )

• occurs in mice by 24 weeks of age

abnormal intestinal epithelium morphology ( J:29999 )

• crypt hyperplasia and unusual branching is observed

rectal prolapse ( J:29999 )

• occasional occurrence among mice whom live past 9 weeks of age

colitis ( J:29999 )

• occurs in all mice that survive past 9 weeks of age, with thickening of large intestinal wall

cardiovascular system

rectal hemorrhage ( J:29999 )

• is rarely observed

growth/size/body

cachexia ( J:29999 )

• weight loss resulting from intestinal inflammation is observed by 24 weeks

hematopoietic system

anemia ( J:29999 )

• occurs in mice 24 weeks of age

behavior/neurological

hunched posture ( J:29999 )

• occurs in mice 24 weeks of age

cellular

abnormal intestinal goblet cell morphology ( J:29999 )

• loss of mucin is observed in goblet cells

Genotype
MGI:3759416

cx14

• Allelic Composition: Il2^tm1Hor/Il2^tm1Hor; Rag2^tm1Fwa/Rag2^tm1Fwa
• Genetic Background: involves: 129P2/OlaHsd * 129S/SvEv * C57BL/6

immune system

immune system phenotype ( J:29999 )

N • colitis nor associated changes in intestinal architecture are not observed in these mice, suggesting mature lymphocytes propogate colitis in mice lacking expression of IL2

hematopoietic system

abnormal blood cell morphology/development ( J:29999 )

• no anemia is observed in these animals

Genotype
MGI:4843436

cx15

• Allelic Composition: Il2^tm1Hor/Il2^tm1Hor; Rag2^tm1Fwa/Rag2^tm1Fwa; Tg(Tcra5CC7,Tcrb5CC7)IWep/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/10

hematopoietic system

abnormal T cell number ( J:120176 )

• decreased proportion of IFN-gamma-producing cells in draining lymph nodes after adoptive transfer nae T cells

increased T-helper 17 cell number ( J:120176 )

• increase in the percentage of IL-17-producing cells in culturing CD4+ T cells in vitro under Th17-polarizing conditions

• produce more than twice as many Th17 cells in draining lymph nodes after adoptive transfer naive T cells

immune system

abnormal T cell number ( J:120176 )

• decreased proportion of IFN-gamma-producing cells in draining lymph nodes after adoptive transfer nae T cells

increased T-helper 17 cell number ( J:120176 )

• increase in the percentage of IL-17-producing cells in culturing CD4+ T cells in vitro under Th17-polarizing conditions

• produce more than twice as many Th17 cells in draining lymph nodes after adoptive transfer naive T cells

Genotype
MGI:3759409

cx16

• Allelic Composition: Il2^tm1Hor/Il2^tm1Hor; Il4^tm1Cgn/Il4^tm1Cgn
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

cellular

increased B cell proliferation ( J:16662 )

• B cells from lymph nodes have a larger size, and incorporate more BrdU indicating a faster proliferation rate

increased T cell proliferation ( J:16662 )

• 2-10 fold higher using in vivo incorporation of BrdU, which indicates a faster proliferation rate

immune system

increased B cell proliferation ( J:16662 )

• B cells from lymph nodes have a larger size, and incorporate more BrdU indicating a faster proliferation rate

increased T cell proliferation ( J:16662 )

• 2-10 fold higher using in vivo incorporation of BrdU, which indicates a faster proliferation rate

increased pro-B cell number ( J:16662 )

• found in bone marrow

increased pre-B cell number ( J:16662 )

• found in bone marrow

decreased IgG level ( J:16662 , J:26861 )

• there are decreased levels of viral specific antibodies 9 days after infection with lymphocytic choriomeningitis virus (J:16662)

• serum levels of IgG and IgE are close to normal in uninfected mice, compared to the high levels of these immunoglobulins found in mice with just the mutant Il2 locus (J:16662)

decreased cytotoxic T cell cytolysis ( J:26861 )

• there is a nine fold reduction of target cell killing by primary T cells in a chromium release assay

• there is no target cell killing by previously stimulated T cells in a chromium release assay

• footpad swelling is strongly reduced 6-10 days after infection with lymphocytic choriomeningitis virus

abnormal susceptibility to Riboviria infection ( J:26861 )

• despite reduced cytotoxic T cell activity, mice still eliminate lymphocytic choriomeningitis virus within nine days of infection

hematopoietic system

increased B cell proliferation ( J:16662 )

• B cells from lymph nodes have a larger size, and incorporate more BrdU indicating a faster proliferation rate

increased T cell proliferation ( J:16662 )

• 2-10 fold higher using in vivo incorporation of BrdU, which indicates a faster proliferation rate

increased pro-B cell number ( J:16662 )

• found in bone marrow

increased pre-B cell number ( J:16662 )

• found in bone marrow

decreased IgG level ( J:16662 , J:26861 )

• there are decreased levels of viral specific antibodies 9 days after infection with lymphocytic choriomeningitis virus (J:16662)

• serum levels of IgG and IgE are close to normal in uninfected mice, compared to the high levels of these immunoglobulins found in mice with just the mutant Il2 locus (J:16662)

decreased cytotoxic T cell cytolysis ( J:26861 )

• there is a nine fold reduction of target cell killing by primary T cells in a chromium release assay

• there is no target cell killing by previously stimulated T cells in a chromium release assay

• footpad swelling is strongly reduced 6-10 days after infection with lymphocytic choriomeningitis virus

Genotype
MGI:4843515

cx17

• Allelic Composition: Il2^tm1Hor/Il2^tm1Hor; Tcrb^tm1Mom/Tcrb^tm1Mom
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

digestive/alimentary system

digestive/alimentary phenotype ( J:135589 )

N • unlike Tcra^tm1Mom homozygotes, mice do not develop colitis

immune system

immune system phenotype ( J:135589 )

N • unlike Tcra^tm1Mom homozygotes, mice do not develop colitis

Genotype
MGI:3759414

cx18

• Allelic Composition: Igh-J^tm1Dhu/Igh-J⁺; Il2^tm1Hor/Il2^tm1Hor
• Genetic Background: involves: 129/Sv * C57BL/6

immune system

colitis ( J:29999 )

• occurs in all mice that survive past 9 weeks of age, with thickening of large intestinal wall

enlarged mesenteric lymph nodes ( J:29999 )

• are increased 3-10 fold in size as compared to control littermates

digestive/alimentary system

rectal hemorrhage ( J:29999 )

• is rarely observed

abnormal intestinal goblet cell morphology ( J:29999 )

• loss of mucin is observed in goblet cells

diarrhea ( J:29999 )

• occurs in mice 24 weeks of age

abnormal intestinal epithelium morphology ( J:29999 )

• crypt hyperplasia and unusual branching is observed

rectal prolapse ( J:29999 )

• occasional occurrence among mice whom live past 9 weeks of age

colitis ( J:29999 )

• occurs in all mice that survive past 9 weeks of age, with thickening of large intestinal wall

cardiovascular system

rectal hemorrhage ( J:29999 )

• is rarely observed

growth/size/body

cachexia ( J:29999 )

• weight loss resulting from intestinal inflammation is observed by 24 weeks

hematopoietic system

anemia ( J:29999 )

• occurs in mice 24 weeks of age

behavior/neurological

hunched posture ( J:29999 )

• occurs in mice 24 weeks of age

cellular

abnormal intestinal goblet cell morphology ( J:29999 )

• loss of mucin is observed in goblet cells

Genotype
MGI:3759413

cx19

• Allelic Composition: Igh-J^tm1Dhu/Igh-J^tm1Dhu; Il2^tm1Hor/Il2^tm1Hor
• Genetic Background: involves: 129/Sv * C57BL/6

immune system

colitis ( J:29999 )

• occurs in all mice that survive past 9 weeks of age, with thickening of large intestinal wall

enlarged mesenteric lymph nodes ( J:29999 )

• are increased 3-10 fold in size as compared to control littermates

digestive/alimentary system

rectal hemorrhage ( J:29999 )

• is rarely observed

abnormal intestinal goblet cell morphology ( J:29999 )

• loss of mucin is observed in goblet cells

diarrhea ( J:29999 )

• occurs in mice 24 weeks of age

abnormal intestinal epithelium morphology ( J:29999 )

• crypt hyperplasia and unusual branching is observed

rectal prolapse ( J:29999 )

• occasional occurrence among mice whom live past 9 weeks of age

colitis ( J:29999 )

• occurs in all mice that survive past 9 weeks of age, with thickening of large intestinal wall

cardiovascular system

rectal hemorrhage ( J:29999 )

• is rarely observed

growth/size/body

cachexia ( J:29999 )

• weight loss resulting from intestinal inflammation is observed by 24 weeks

hematopoietic system

abnormal blood cell morphology/development ( J:29999 )

• : hemocrit levels are near normal (36% mean), suggesting B cells contribute to the anemia observed in mice lacking IL2 expression

behavior/neurological

hunched posture ( J:29999 )

• occurs in mice 24 weeks of age

cellular

abnormal intestinal goblet cell morphology ( J:29999 )

• loss of mucin is observed in goblet cells