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

View All References

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
involves: 129P2/OlaHsd * C57BL/6

behavior/neurological phenotype

hunched posture
- occurs in mice 24 weeks of age

digestive/alimentary phenotype

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

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

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

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
- infiltrating lymphocytes sometimes form nodules
- Normal - mice bred in a germ-free facility do not display any histopathological signs of 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
- occurs in all mice that survive past 9 weeks of age, with thickening of large intestinal wall

crypts of Lieberkuhn abscesses
- frequently occurres in the large intestine

diarrhea
- occurs in mice 24 weeks of age

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

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

mortality/aging

premature death
- 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

cardiovascular system phenotype

rectal hemorrhage
- rarely observed

cellular phenotype

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

decreased splenocyte proliferation
- poor proliferative response to anti-CD3 antibody is partially rescued by addition of cytokines including IL-2, IL-4, IL-7
- proliferative response of splenocytes to anti-CD3 antibody is only 16% of wt controls
- there is reduced proliferation to allogenic leukocytes

decreased T cell proliferation

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

endocrine/exocrine gland phenotype

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

abnormal thymocyte activation
- Normal - however, treatment with an IL-12 neutralizing antibody normalized the percentage of activated thymocytes
- 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

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
- Normal - however, IgM levels are in vivo are normal
- 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
- unable to induce IgM secretion from activated B cells in an in vitro assay

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

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

abnormal cytotoxic T cell physiology
- 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

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

abnormal lymphocyte cell number

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

abnormal lymphocyte physiology

abnormal T-helper 1 cell differentiation
- 10 fold greater amounts of IFN gamma were made by thymocytes from immunized mutant mice as measured by an in vitro assay
- 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

abnormal thymocyte activation
- Normal - however, treatment with an IL-12 neutralizing antibody normalized the percentage of activated thymocytes
- 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

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

decreased cytotoxic T cell cytolysis
- 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 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

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

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
- poor proliferative response to anti-CD3 antibody is partially rescued by addition of cytokines including IL-2, IL-4, IL-7
- proliferative response of splenocytes to anti-CD3 antibody is only 16% of wt controls
- there is reduced proliferation to allogenic leukocytes

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

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

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

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

increased IgG2a level
- levels of IgG2a are also elevated

increased IgG2b level
- levels of IgG2b are also elevated

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

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

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 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

homeostasis/metabolism phenotype

amyloidosis
- predominately in liver, spleen, and kidneys

immune system phenotype

abnormal CD4-positive, alpha-beta T cell physiology
- Normal - however, IgM levels are in vivo are normal
- 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
- unable to induce IgM secretion from activated B cells in an in vitro assay

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

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

abnormal cytotoxic T cell physiology
- 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

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

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

abnormal lymphocyte cell number

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

abnormal lymphocyte physiology

abnormal T-helper 1 cell differentiation
- 10 fold greater amounts of IFN gamma were made by thymocytes from immunized mutant mice as measured by an in vitro assay
- 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

abnormal thymocyte activation
- Normal - however, treatment with an IL-12 neutralizing antibody normalized the percentage of activated thymocytes
- 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

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

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
- infiltrating lymphocytes sometimes form nodules
- Normal - mice bred in a germ-free facility do not display any histopathological signs of 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
- occurs in all mice that survive past 9 weeks of age, with thickening of large intestinal wall

decreased cytotoxic T cell cytolysis
- 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 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

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

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
- poor proliferative response to anti-CD3 antibody is partially rescued by addition of cytokines including IL-2, IL-4, IL-7
- proliferative response of splenocytes to anti-CD3 antibody is only 16% of wt controls
- there is reduced proliferation to allogenic leukocytes

decreased T cell proliferation

enlarged lymph nodes

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

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

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

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

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

increased IgG2a level
- levels of IgG2a are also elevated

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

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

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

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

lymph node hyperplasia

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

cardiovascular system phenotype

heart inflammation
- moderate to severe inflammation noted upon necropsy

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

homeostasis/metabolism phenotype

increased circulating bilirubin level

immune system phenotype

abnormal lymphocyte morphology

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

abnormal spleen morphology

enlarged lymph nodes

heart inflammation
- moderate to severe inflammation noted upon necropsy

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

increased germinal center B cell number

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

increased inflammatory response

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

increased spleen red pulp amount

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 T cell proliferation
- 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)

liver inflammation

lung inflammation
- moderate to severe inflammation noted upon necropsy

pancreas inflammation
- moderate to severe inflammation noted upon necropsy

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

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

cellular phenotype

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

increased T cell proliferation
- 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)

liver/biliary system phenotype

liver inflammation

mortality/aging

premature death
- 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
- 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

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

hematopoietic system phenotype

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

abnormal lymphocyte morphology

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

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

abnormal spleen morphology

decreased hematocrit

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

increased germinal center B cell number

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

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

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

increased spleen red pulp amount

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 T cell proliferation
- 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)

low mean erythrocyte cell number

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

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

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

increased T cell number

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 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

increased T cell number

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

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

cellular phenotype

abnormal cellular respiration
- fail to switch from oxidative phosphorylation to aerobic glycolysis after 5 days of tamoxifen treatment and 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

endocrine/exocrine gland phenotype

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

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

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

hematopoietic system phenotype

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

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

increased splenocyte number

homeostasis/metabolism phenotype

abnormal circulating cytokine level

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

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

digestive/alimentary phenotype

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

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

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

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

immune system phenotype

abnormal circulating cytokine level

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

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

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

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

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

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

increased splenocyte number

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

lacrimal gland inflammation
- severe inflammation in the lacrimal glands

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

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

vision/eye phenotype

lacrimal gland inflammation
- severe inflammation in the lacrimal glands

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

homeostasis/metabolism phenotype

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

immune system phenotype

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

increased T-helper 17 cell number
- 30-fold difference in absolute numbers of mesenteric Th17 cells compared with wild-type mice
- 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

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

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

hematopoietic 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

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

JAX® Mice, Products & Services Conditions of Use

"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCT(S)" means biological materials supplied by JACKSON, and their derivatives. "SERVICES" means projects conducted by JACKSON for other parties that may include but are not limited to the use of MICE or PRODUCTS. "RECIPIENT" means each recipient of MICE, PRODUCTS, or SERVICES provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE, PRODUCTS or SERVICES from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON’s prior written authorization.

No Warranty

MICE, PRODUCTS AND SERVICES ARE PROVIDED "AS IS". JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.

Credit for PRODUCTS or SERVICES

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of, PRODUCTS or SERVICES, JACKSON will, at its option, provide credit or replacement for the PRODUCT received or the SERVICES provided; JACKSON makes no other representations and this shall be the exclusive remedy of the purchaser. Please note specific policy for live mice.

Animal Care and Use for SERVICES

Consistent with the requirement for a written understanding regarding animal care and use, the JACKSON Animal Care and Use Committee will review the animal care and use protocol(s) associated with any SERVICES to be performed at JACKSON, and JACKSON shall have ultimate responsibility and authority for the care of animals while on site or in JACKSON custody.

No Liability

In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS, or SERVICES, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS, or SERVICES from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.

MICE, PRODUCTS or SERVICES are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or SERVICES. In addition, special terms and conditions of sale of certain MICE, PRODUCTS, or SERVICES may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and SERVICES by JACKSON, and by its licensees and distributors.

Acceptance of delivery of MICE, PRODUCTS or SERVICES shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or SERVICES by JACKSON.

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/Il2tm1Horinvolves: 129P2/OlaHsd * C57BL/6

behavior/neurological phenotype

digestive/alimentary phenotype

mortality/aging

cardiovascular system phenotype

cellular phenotype

endocrine/exocrine gland phenotype

growth/size/body region phenotype

hematopoietic system phenotype

homeostasis/metabolism phenotype

immune system phenotype

Genotype: Il2tm1Hor/Il2tm1HorC.129P2-Il2

cardiovascular system phenotype

homeostasis/metabolism phenotype

immune system phenotype

cellular phenotype

liver/biliary system phenotype

mortality/aging

respiratory system phenotype

endocrine/exocrine gland phenotype

growth/size/body region phenotype

hematopoietic system phenotype

Genotype: Il2tm1Hor/Il2tm1HorB6.129P2-Il2

cellular phenotype

mammalian phenotype

hematopoietic system phenotype

immune system phenotype

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

cellular phenotype

endocrine/exocrine gland phenotype

hematopoietic system phenotype

homeostasis/metabolism phenotype

digestive/alimentary phenotype

immune system phenotype

vision/eye 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/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

JAX® Mice, Products & Services Conditions of Use

No Warranty

Also Known As:IL-2^-

Il2^tm1Hor

Allele Symbol: Il2^tm1Hor

Genotype: Il2^tm1Hor related

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

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

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

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

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

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

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

Additional - Il2^tm1Hor related