Overview

Also Known As:IL-2^-

These IL-2 knock-out mice exhibit an impaired response to polyclonal T cell activators, deficits in their helper function, and a reduction in natural killer cell activity.

Donating Investigator

Dr. Ivan Horak, Forschungs institut fur Molekulare

Genetic overview

Genetic Background	Generation
000659 C3H/HeJ

Il2^tm1Hor

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Il2	interleukin 2

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Research Applications

Immunology, Inflammation and Autoimmunity Research
Cancer Research
Hematological Research

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Details

Detailed Description

Homozygous mutant mice for the Il2^tm1Hor targeted mutation show no apparent deficit in thymocyte differentiation or selection, types and numbers of T cells from spleens and lymph nodes are comparable to those of wildtype. They do have an impaired response to polyclonal T cell activators in the absence of additional IL2, deficits in their helper function and a reduction in natural killer cell activity. There is significant pre-weaning and post-weaning loss of homozygotes on the BALB/c, C3H/HeJCrlBR and C57BL/6J genetic backgrounds. In addition, homozygous mice develop inflammatory bowel disease between 6 and 15 weeks of age and reportedly die within 10-25 weeks under conventional housing conditions. Homozygotes on the C57BL/6J genetic background show an atrophied pancreas with apparently intact islets. Homozygotes on the BALB/c genetic background do not develop inflammatory bowel disease symptoms but rather die 3-5 weeks postnatally of a form of hemolytic anemia. For a more detailed description please refer to the JAX Notes Fall 1996 article.

Control Suggestions

Wild-type from the colony
000659 C3H/HeJ

Additional Information

Considerations for Choosing Controls

Selected References

Schorle H; Holtschke T; Hunig T; Schimpl A; Horak I. 1991. Development and function of T cells in mice rendered interleukin-2 deficient by gene targeting. Nature 352(6336):621-4PubMed: 1830926 MGI: J:39989

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Genetics

Il2^tm1Hor

Allele Symbol: Il2^tm1Hor

Allele Name	targeted mutation 1, Ivan Horak
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	IL-2-; Il2-; IL-2 KO; IL-2^null
Gene Symbol and Name	Il2, interleukin 2
Gene Synonym(s)
Strain of Origin	129P2/OlaHsd
Chromosome	3
Molecular Note	Insertion of a neomycin-resistance gene into the third exon introduced several stop codons in all reading frames.
Mutations Made By	Dr. Ivan Horak, Forschungs institut fur Molekulare

Disease/Phenotype

Disease Terms

Models with phenotypic similarity to human diseases where etiology is unknown or involving genes where ortholog is unknown.

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Immunology, Inflammation and Autoimmunity Research
- Inflammation
  - Inflammatory bowel disease

Genotype: Il2^tm1Hor related

Cancer Research
- Growth Factors/Receptors/Cytokines
Hematological Research
- Immunological Defects
- Anemia, Iron Deficiency and Transport Defects
  - hemolytic
Immunology, Inflammation and Autoimmunity Research
- Growth Factors/Receptors/Cytokines
- Autoimmunity
  - hemolytic anemia

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Il2^tm1Hor/Il2^tm1Hor
C.129P2-Il2

cardiovascular system phenotype

heart inflammation
- moderate to severe inflammation noted upon necropsy

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

hematopoietic system phenotype

abnormal regulatory T cell physiology
- there is a rapid loss of adoptively transferred regulatory T cells

increased mean corpuscular hemoglobin
- about twice normal levels, this indicates a hyperchromic anemia

increased T cell proliferation
- CD4 T cells are activated prior to CD8 T cells (10 days vs. 15 days of age)
- by 10 days of age, T cells in lymph nodes express high levels of activation markers and are proliferating at an increased rate

abnormal reticulocyte morphology
- marked reduction concurrent with T cell invasion of marrow

increased B cell proliferation
- faster proliferation as measured by BrdU incorporation

increased plasma cell number
- seen in the spleen by 15 days of age

low mean erythrocyte cell number

spleen hyperplasia
- 15 day old mice exhibit hyperplasia of the white pulp

abnormal bone marrow cell number
- invasion of T cells occur, with a concurrent drop in B cells and other nucleated cells

abnormal lymphocyte morphology

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

increased spleen red pulp amount

abnormal spleen morphology

increased susceptibility to autoimmune hemolytic anemia
- 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

increased germinal center B cell number

decreased hematocrit

homeostasis/metabolism phenotype

increased circulating bilirubin level

cellular phenotype

increased B cell proliferation
- faster proliferation as measured by BrdU incorporation

increased T cell proliferation
- CD4 T cells are activated prior to CD8 T cells (10 days vs. 15 days of age)
- by 10 days of age, T cells in lymph nodes express high levels of activation markers and are proliferating at an increased rate

immune system phenotype

increased germinal center B cell number

increased T cell proliferation
- CD4 T cells are activated prior to CD8 T cells (10 days vs. 15 days of age)
- by 10 days of age, T cells in lymph nodes express high levels of activation markers and are proliferating at an increased rate

abnormal lymphocyte morphology

abnormal regulatory T cell physiology
- there is a rapid loss of adoptively transferred regulatory T cells

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

heart inflammation
- moderate to severe inflammation noted upon necropsy

increased B cell proliferation
- faster proliferation as measured by BrdU incorporation

lung inflammation
- moderate to severe inflammation noted upon necropsy

spleen hyperplasia
- 15 day old mice exhibit hyperplasia of the white pulp

increased plasma cell number
- seen in the spleen by 15 days of age

increased susceptibility to autoimmune hemolytic anemia
- 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

pancreas inflammation
- moderate to severe inflammation noted upon necropsy

enlarged lymph nodes

abnormal spleen morphology

liver inflammation

increased spleen red pulp amount

increased inflammatory response

liver/biliary system phenotype

liver inflammation

mortality/aging

premature death
- mice all die by 5 weeks of age, compared to death by 25 weeks of age for mice with the same mutant locus on a mixed genetic background
- 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

respiratory system phenotype

lung inflammation
- moderate to severe inflammation noted upon necropsy

endocrine/exocrine gland phenotype

pancreas inflammation
- moderate to severe inflammation noted upon necropsy

growth/size/body region phenotype

spleen hyperplasia
- 15 day old mice exhibit hyperplasia of the white pulp

Genotype: Il2^tm1Hor/Il2^tm1Hor
involves: 129P2/OlaHsd

hematopoietic system phenotype

increased regulatory T cell number
- of CD25^lo regulatory T cells

immune system phenotype

increased regulatory T cell number
- of CD25^lo regulatory T cells

mammalian phenotype

reproductive system phenotype
- 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: Il2^tm1Hor/Il2^tm1Hor
involves: 129P2/OlaHsd * C57BL/6J

hematopoietic system phenotype

increased T-helper 17 cell number
- greater proportion of IL-17-positive cells (most of which CD4 positive) in peripheral lymph nodes
- increase in the percentage of IL-17-producing cells in culturing CD4+ T cells in vitro under Th17-polarizing conditions
- 30-fold difference in absolute numbers of mesenteric Th17 cells compared with wild-type mice

homeostasis/metabolism phenotype

increased circulating interleukin-17 level
- elevated serum IL-17 concentration at 3 months old

immune system phenotype

increased T-helper 17 cell number
- greater proportion of IL-17-positive cells (most of which CD4 positive) in peripheral lymph nodes
- increase in the percentage of IL-17-producing cells in culturing CD4+ T cells in vitro under Th17-polarizing conditions
- 30-fold difference in absolute numbers of mesenteric Th17 cells compared with wild-type mice

increased circulating interleukin-17 level
- elevated serum IL-17 concentration at 3 months old

Genotype: Il2^tm1Hor/Il2^tm1Hor
B6.129P2-Il2/J

endocrine/exocrine gland phenotype

abnormal salivary gland duct morphology
- mild ductal changes in the salivary gland

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

abnormal salivary gland morphology
- severe acinar gland destruction

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

lacrimal gland inflammation
- severe inflammation in the lacrimal glands

cellular phenotype

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

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

hematopoietic system phenotype

decreased CD4-positive, CD25-positive, alpha-beta regulatory T cell number
- 4-fold

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

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

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

increased splenocyte number

increased CD4-positive, alpha beta T cell number
- 3-fold

homeostasis/metabolism phenotype

abnormal circulating cytokine level

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

decreased circulating interferon-gamma level
- after activation with anti-CD3/28

decreased circulating interleukin-13 level
- after activation with anti-CD3/28

decreased circulating interleukin-4 level
- after activation with anti-CD3/28

immune system phenotype

abnormal response to transplant
- wild-type regulatory T cells fail to engraft when adoptively transferred into these mice

decreased circulating interleukin-13 level
- after activation with anti-CD3/28

salivary gland inflammation
- severe inflammation in the salivary glands
- although more Gr-1+ cells are seen in the salivary glands, the absolute number of neutrophils is relatively small
- salivary glands show presence of a large fraction of T cells and a ratio of CD4+/CD8+ of 1/2
- major population of infiltrating leukocytes are lymphocytes and to a much lower extent neutrophils

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

increased splenocyte number

decreased circulating interferon-gamma level
- after activation with anti-CD3/28

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

increased CD4-positive, alpha beta T cell number
- 3-fold

large intestinal inflammation
- severe inflammation in the colon
- Normal - however, mice do show severe inflammation in the lung or the skin

increased susceptibility to autoimmune disorder
- transfer of wild-type regulatory T cells did not prevent autoimmune disorder
- generalized symptoms of autoimmunity noted at 4 weeks of age

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

lacrimal gland inflammation
- severe inflammation in the lacrimal glands

decreased circulating interleukin-4 level
- after activation with anti-CD3/28

decreased CD4-positive, CD25-positive, alpha-beta regulatory T cell number
- 4-fold

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

abnormal circulating cytokine level

digestive/alimentary phenotype

abnormal salivary gland morphology
- severe acinar gland destruction

large intestinal inflammation
- Normal - however, mice do show severe inflammation in the lung or the skin
- severe inflammation in the colon

abnormal salivary gland duct morphology
- mild ductal changes in the salivary gland

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

vision/eye phenotype

lacrimal gland inflammation
- severe inflammation in the lacrimal glands

Genotype: Il2^tm1Hor/Il2^tm1Hor
B6.129P2-Il2

cellular phenotype

increased T cell proliferation
- T cells continue to respond to antigen instead of going into anergy during secondary stimulation with antigens

mammalian phenotype

immune system phenotype
- Normal - 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
- Normal - marrow chimeras

hematopoietic system phenotype

increased CD8-positive, alpha-beta T cell number
- activated T cell numbers decrease with slower kinetics than wild-type mice after after immunization with staphylococcal enterotoxin

increased T cell number

increased CD4-positive, alpha beta T cell number
- activated T cell numbers fail to decrease to normal levels after immunization with staphylococcal enterotoxin, indicating a problem with peripheral deletion

increased activated T cell number
- higher numbers due to less sensitivity to Fas-mediated cell death (apoptosis)

increased T cell proliferation
- T cells continue to respond to antigen instead of going into anergy during secondary stimulation with antigens

immune system phenotype

increased activated T cell number
- higher numbers due to less sensitivity to Fas-mediated cell death (apoptosis)

increased CD8-positive, alpha-beta T cell number
- activated T cell numbers decrease with slower kinetics than wild-type mice after after immunization with staphylococcal enterotoxin

increased T cell proliferation
- T cells continue to respond to antigen instead of going into anergy during secondary stimulation with antigens

increased CD4-positive, alpha beta T cell number
- activated T cell numbers fail to decrease to normal levels after immunization with staphylococcal enterotoxin, indicating a problem with peripheral deletion

increased T cell number

Genotype: Il2^tm1Hor/Il2^tm1Hor
involves: 129P2/OlaHsd * C57BL/6

behavior/neurological phenotype

hunched posture
- occurs in mice 24 weeks of age

cellular phenotype

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

increased T cell proliferation
- 2-10 fold higher using in vivo incorporation of BrdU, which indicates a faster proliferation rate
- the proliferation of T cells in the colon is twice that of wild-type controls

decreased splenocyte proliferation
- 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
- proliferative response of splenocytes to anti-CD3 antibody is only 16% of wt controls

abnormal colon goblet cell morphology
- loss of mucin is observed in goblet cells
- colon epithelium shows loss of goblet cells

decreased T cell proliferation

mortality/aging

premature death
- the remaining mice die by 25 weeks of age from inflammatory bowel disease
- about of 50% of mice die within the first 9 weeks of age with enlarged lymphoid organs and severe anemia

digestive/alimentary phenotype

abnormal intestinal epithelium morphology
- crypt hyperplasia and unusual branching is observed
- prominent epithelial regeneration with crypt branching and dysplasia near areas of inflammation

colitis
- Normal - 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
- infiltrating lymphocytes sometimes form nodules
- Normal - mice bred in a germ-free facility do not display any histopathological signs of colitis
- occurs in all mice that survive past 9 weeks of age, with thickening of large intestinal wall
- mice kept under a specific pathogen free environment develop colitis when immunized with an antigen that activates CD4 T cells
- 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

diarrhea
- occurs in mice 24 weeks of age

rectal hemorrhage
- rarely observed

rectal prolapse
- frequent occurrence among mice whom live past 9 weeks of age
- occasional occurrence among mice whom live past 9 weeks of age

abnormal colon goblet cell morphology
- colon epithelium shows loss of goblet cells
- loss of mucin is observed in goblet cells

intestinal ulcer
- ulcers occur in the large intestine, with pronounced thickening of the bowel wall

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

crypts of Lieberkuhn abscesses
- frequently occurres in the large intestine

cardiovascular system phenotype

rectal hemorrhage
- rarely observed

endocrine/exocrine gland phenotype

abnormal thymocyte activation
- in vitro proliferation is reduced in presence of concanavalin A or anti-CD3 antibody
- Normal - however, treatment with an IL-12 neutralizing antibody normalized the percentage of activated thymocytes
- increased activation of thymocytes 7 days after immunization with a CD4 T cell activating antigen, as measured by expression of CD69 and Icam1

abnormal colon goblet cell morphology
- colon epithelium shows loss of goblet cells
- loss of mucin is observed in goblet cells

crypts of Lieberkuhn abscesses
- frequently occurres in the large intestine

growth/size/body region phenotype

cachexia
- weight loss resulting from intestinal inflammation is observed by 24 weeks

enlarged spleen
- occurs in the 50% of mice that die prematurely

hematopoietic system phenotype

abnormal CD4-positive, alpha-beta T cell physiology
- increased cytotoxic effectiveness of CD4 T cells isolated from the colon
- there is an impaired ability to induce Ig class switching in B cells after infection with vesicular stomatitis virus
- Normal - however, IgM levels are in vivo are normal
- unable to induce IgM secretion from activated B cells in an in vitro assay

abnormal class switch recombination
- there is delayed class switching from IgM to IgG after infection with vesicular stomatitis virus

decreased T cell proliferation

abnormal CD8 positive, alpha-beta intraepithelial T cell morphology
- T cells expressing the CD8 alpha-beta heterodimer predominate over CD8 alpha-alpha T cells
- increased number (5-100 fold) are found in diseased colon

abnormal gamma-delta intraepithelial T cell morphology
- decreased percentage of these cells are found in the colon epithelium

abnormal T-helper 1 cell differentiation
- Normal - however, treatment with an IL-12 neutralizing antibody normalized Th1cytokine levels
- 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

anemia
- occurs in mice 24 weeks of age
- severe anemia is found in 50% of mice that die prematurely

decreased cytotoxic T cell cytolysis
- there is a three fold reduction of target cell killing by primary T cells in a chromium release assay
- footpad swelling is reduced 6-10 days after infection with lymphocytic choriomeningitis virus
- no target cell killing by previously stimulated T cells in a chromium release assay
- there is reduced killing of allogeneic tumor cells in an in vitro assay

decreased splenocyte proliferation
- 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

increased T cell proliferation
- 2-10 fold higher using in vivo incorporation of BrdU, which indicates a faster proliferation rate
- the proliferation of T cells in the colon is twice that of wild-type controls

increased double-negative T cell number
- 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

increased IgG1 level
- levels of IgG1 are increased 100 fold
- levels of IgG1 are drastically increased to levels above 2700 ug/ml
- drastic elevation in secretion of IgG1 by B cells found in the colon

increased IgG2b level
- levels of IgG2b are also elevated

abnormal thymocyte activation
- in vitro proliferation is reduced in presence of concanavalin A or anti-CD3 antibody
- Normal - however, treatment with an IL-12 neutralizing antibody normalized the percentage of activated thymocytes
- increased activation of thymocytes 7 days after immunization with a CD4 T cell activating antigen, as measured by expression of CD69 and Icam1

increased IgE level
- levels are 10 fold higher than those observed in wild-type mice

increased IgA level
- drastic elevation in secretion by B cells found in the colon

abnormal lymphocyte cell number

enlarged spleen
- occurs in the 50% of mice that die prematurely

increased pre-B cell number
- of cells in the bone marrow

abnormal cytotoxic T cell physiology
- enhanced target cell killing by intraepithelial lymphocytes T cells (IEL) of the small intestine
- enhanced target cell killing by intraepithelial lymphocytes T cells (IEL) and lamina propia lymphocytes of the large intestine

abnormal lymphocyte physiology

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

increased single-positive T cell number
- Normal - however, treatment with an IL-12 neutralizing antibody normalized SP cell numbers
- 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

increased pro-B cell number
- of cells in the bone marrow

increased IgG2a level
- levels of IgG2a are also elevated

decreased double-positive T cell number
- 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

decreased double-negative T cell number
- there is a drastic reduction in the colon

abnormal lymphocyte morphology
- decreased apoptosis in thymus upon injection with anti-CD3 antibody

impaired natural killer cell mediated cytotoxicity
- 3 to 9 fold reduction in killing of NK susceptible target cells as measured by chromium release assay

homeostasis/metabolism phenotype

amyloidosis
- predominately in liver, spleen, and kidneys

immune system phenotype

abnormal cytotoxic T cell physiology
- enhanced target cell killing by intraepithelial lymphocytes T cells (IEL) of the small intestine
- enhanced target cell killing by intraepithelial lymphocytes T cells (IEL) and lamina propia lymphocytes of the large intestine

abnormal susceptibility to Riboviria infection
- Normal - despite reduced cytotoxic T cell activity, mice still clear lymphocytic choriomeningitis virus within nine days of infection

decreased double-positive T cell number
- 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

decreased splenocyte proliferation
- there is reduced proliferation to allogenic leukocytes
- 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

enlarged lymph nodes

increased IgG1 level
- levels of IgG1 are increased 100 fold
- levels of IgG1 are drastically increased to levels above 2700 ug/ml
- drastic elevation in secretion of IgG1 by B cells found in the colon

increased pre-B cell number
- of cells in the bone marrow

increased pro-B cell number
- of cells in the bone marrow

abnormal level of surface class II molecules
- expression occurs in high number of colon epithelial cells

abnormal T-helper 1 cell differentiation
- Normal - however, treatment with an IL-12 neutralizing antibody normalized Th1cytokine levels
- low levels of the Th2 cytokine IL-4 were made compared to the large level made by wt thymocytes
- 10 fold greater amounts of IFN gamma were made by thymocytes from immunized mutant mice as measured by an in vitro assay

colitis
- occurs in all mice that survive past 9 weeks of age, with thickening of large intestinal wall
- infiltrating lymphocytes sometimes form nodules
- Normal - mice bred in a germ-free facility do not display any histopathological signs of colitis
- 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
- Normal - 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
- mice kept under a specific pathogen free environment develop colitis when immunized with an antigen that activates CD4 T cells

abnormal lymphocyte physiology

increased single-positive T cell number
- 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
- Normal - however, treatment with an IL-12 neutralizing antibody normalized SP cell numbers

lymph node hyperplasia

decreased T cell proliferation

enlarged spleen
- occurs in the 50% of mice that die prematurely

impaired natural killer cell mediated cytotoxicity
- 3 to 9 fold reduction in killing of NK susceptible target cells as measured by chromium release assay

increased double-negative T cell number
- 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

increased IgG2b level
- levels of IgG2b are also elevated

increased length of allograft survival
- graft rejection of allogeneic pancreatic islet cells is delayed by 11 days compared to controls

increased T cell proliferation
- 2-10 fold higher using in vivo incorporation of BrdU, which indicates a faster proliferation rate
- the proliferation of T cells in the colon is twice that of wild-type controls

abnormal CD4-positive, alpha-beta T cell physiology
- there is an impaired ability to induce Ig class switching in B cells after infection with vesicular stomatitis virus
- Normal - however, IgM levels are in vivo are normal
- increased cytotoxic effectiveness of CD4 T cells isolated from the colon
- unable to induce IgM secretion from activated B cells in an in vitro assay

abnormal thymocyte activation
- in vitro proliferation is reduced in presence of concanavalin A or anti-CD3 antibody
- increased activation of thymocytes 7 days after immunization with a CD4 T cell activating antigen, as measured by expression of CD69 and Icam1
- Normal - however, treatment with an IL-12 neutralizing antibody normalized the percentage of activated thymocytes

decreased cytotoxic T cell cytolysis
- there is a three fold reduction of target cell killing by primary T cells in a chromium release assay
- there is reduced killing of allogeneic tumor cells in an in vitro assay
- no target cell killing by previously stimulated T cells in a chromium release assay
- footpad swelling is reduced 6-10 days after infection with lymphocytic choriomeningitis virus

decreased double-negative T cell number
- there is a drastic reduction in the colon

increased IgE level
- levels are 10 fold higher than those observed in wild-type mice

abnormal lymphocyte morphology
- decreased apoptosis in thymus upon injection with anti-CD3 antibody

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

increased IgA level
- drastic elevation in secretion by B cells found in the colon

increased susceptibility to viral infection
- Normal - despite reduced cytotoxic T cell activity, mice still clear lymphocytic choriomeningitis virus within nine days of infection

increased IgG2a level
- levels of IgG2a are also elevated

enlarged mesenteric lymph nodes
- increased 3-10 fold in size as compared to control littermates

abnormal gamma-delta intraepithelial T cell morphology
- decreased percentage of these cells are found in the colon epithelium

abnormal class switch recombination
- there is delayed class switching from IgM to IgG after infection with vesicular stomatitis virus

abnormal CD8 positive, alpha-beta intraepithelial T cell morphology
- T cells expressing the CD8 alpha-beta heterodimer predominate over CD8 alpha-alpha T cells
- increased number (5-100 fold) are found in diseased colon

abnormal lymphocyte cell number

The following phenotype relates to a compound genotype created using this strain

Genotype: Il2^tm1Hor/Il2^tm1Hor
C3.129P2-Il2

hematopoietic system phenotype

increased CD8-positive, alpha-beta T cell number
- activated T cell numbers decrease with slower kinetics than wild-type mice after after immunization with staphylococcal enterotoxin

increased CD4-positive, alpha beta T cell number
- activated T cell numbers fail to decrease to normal levels after immunization with staphylococcal enterotoxin, indicating a problem with peripheral deletion

immune system phenotype

increased CD4-positive, alpha beta T cell number
- 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
- activated T cell numbers decrease with slower kinetics than wild-type mice after after immunization with staphylococcal enterotoxin

References

Schorle H; Holtschke T; Hunig T; Schimpl A; Horak I. 1991. Development and function of T cells in mice rendered interleukin-2 deficient by gene targeting. Nature 352(6336):621-4PubMed: 1830926 MGI: J:39989

Additional References

Antony PA; Paulos CM; Ahmadzadeh M; Akpinarli A; Palmer DC; Sato N; Kaiser A; Hinrichs CS; Klebanoff CA; Tagaya Y; Restifo NP. 2006. Interleukin-2-dependent mechanisms of tolerance and immunity in vivo. J Immunol 176(9):5255-66PubMed: 16621991 MGI: J:115150
Horak I. 1995. Immunodeficiency in IL-2-knockout mice. Clin Immunol Immunopathol 76(3 Pt 2):S172-3PubMed: 7554463 MGI: J:28804
Kundig TM; Schorle H; Bachmann MF; Hengartner H; Zinkernagel RM; Horak I. 1993. Immune responses in interleukin-2-deficient mice. Science 262(5136):1059-61PubMed: 8235625 MGI: J:15573
Sadlack B; Lohler J; Schorle H; Klebb G; Haber H; Sickel E; Noelle RJ; Horak I. 1995. Generalized autoimmune disease in interleukin-2-deficient mice is triggered by an uncontrolled activation and proliferation of CD4+ T cells. Eur J Immunol 25(11):3053-9PubMed: 7489743 MGI: J:29799
Sadlack B; Merz H; Schorle H; Schimpl A; Feller AC; Horak I. 1993. Ulcerative colitis-like disease in mice with a disrupted interleukin-2 gene [see comments] Cell 75(2):253-61PubMed: 8402910 MGI: J:15223

Additional - Il2^tm1Hor related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Il2
- Separated PCR:Il2
- Separated MCA:Il2
- Standard PCR:Il2
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, heterozygous mice may be bred to wildtype siblings, or to C3H/HeJ inbred mice (Stock No. 000659).
- Additional Breeding and Husbandry Support
Appearance
- agouti
  Related Genotype: A/A
Citation
When using the IL-2^- mouse strain in a publication, please cite the originating article(s) and include JAX stock #002228 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
> >	Heterozygous or Wild-type for Il2<tm1Hor>

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

Terms Of Use

General Terms and Conditions

Questions about Terms of Use

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Also Known As:IL-2-

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Control Suggestions

Additional Information

Selected References

Il2tm1Hor

Allele Symbol: Il2tm1Hor

Disease Terms

Models with phenotypic similarity to human diseases where etiology is unknown or involving genes where ortholog is unknown.

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Genotype: Il2tm1Hor related

Mammalian Phenotype Terms by Genotype

Genotype: Il2tm1Hor/Il2tm1HorC.129P2-Il2

cardiovascular system phenotype

hematopoietic system phenotype

homeostasis/metabolism phenotype

cellular phenotype

immune system phenotype

liver/biliary system phenotype

mortality/aging

respiratory system phenotype

endocrine/exocrine gland phenotype

growth/size/body region phenotype

Genotype: Il2tm1Hor/Il2tm1Horinvolves: 129P2/OlaHsd

hematopoietic system phenotype

immune system phenotype

mammalian phenotype

Genotype: Il2tm1Hor/Il2tm1Horinvolves: 129P2/OlaHsd * C57BL/6J

hematopoietic system phenotype

homeostasis/metabolism phenotype

immune system phenotype

Genotype: Il2tm1Hor/Il2tm1HorB6.129P2-Il2/J

endocrine/exocrine gland phenotype

cellular phenotype

hematopoietic system phenotype

homeostasis/metabolism phenotype

immune system phenotype

digestive/alimentary phenotype

vision/eye phenotype

Genotype: Il2tm1Hor/Il2tm1HorB6.129P2-Il2

cellular phenotype

mammalian phenotype

hematopoietic system phenotype

immune system phenotype

Genotype: Il2tm1Hor/Il2tm1Horinvolves: 129P2/OlaHsd * C57BL/6

behavior/neurological phenotype

cellular phenotype

mortality/aging

digestive/alimentary phenotype

cardiovascular system phenotype

endocrine/exocrine gland phenotype

growth/size/body region phenotype

hematopoietic system phenotype

homeostasis/metabolism phenotype

immune system phenotype

Genotype: Il2tm1Hor/Il2tm1HorC3.129P2-Il2

hematopoietic system phenotype

immune system phenotype

References

Additional References

Additional - Il2tm1Hor related

Genotyping Protocols

Breeding Considerations

Appearance

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

Also Known As:IL-2^-

Il2^tm1Hor

Allele Symbol: Il2^tm1Hor

Genotype: Il2^tm1Hor related

Genotype: Il2^tm1Hor/Il2^tm1Hor
C.129P2-Il2

Genotype: Il2^tm1Hor/Il2^tm1Hor
involves: 129P2/OlaHsd

Genotype: Il2^tm1Hor/Il2^tm1Hor
involves: 129P2/OlaHsd * C57BL/6J

Genotype: Il2^tm1Hor/Il2^tm1Hor
B6.129P2-Il2/J

Genotype: Il2^tm1Hor/Il2^tm1Hor
B6.129P2-Il2

Genotype: Il2^tm1Hor/Il2^tm1Hor
involves: 129P2/OlaHsd * C57BL/6

Genotype: Il2^tm1Hor/Il2^tm1Hor
C3.129P2-Il2

Additional - Il2^tm1Hor related