Basic Information

Strain name
C57BL/6-Il2tm1(IL2)Il2ratm1(IL2RA)ll2rbtm2(IL2RB/Bcgen
Common name
B-hIL2/hIL2RA/hIL2RB mice
Catalog number
131076
Background
C57BL/6
Aliases
IL2 also known as TCGF, lymphokine IL2RA also known as CD25, IDDM10, IL2R, IMD41, TCGFR, p55 IL2RB also known as CD122.

Description

Interleukin-2 (IL-2) is a member of a cytokine family, each member of which has a four alpha helix bundle, the family also includes IL-4, IL-7, IL-9, IL-15 and IL-21. IL-2 signals through the IL-2 receptor, a complex consisting of three chains, CD25, CD122 and CD132, which are expressed by lymphocytes. Its affinity for IL2 and cellular function are tightly regulated and vary in different cell types. The low affinity form is a monomer of CD25 which expressed on activated T and B cells, thymocyte subset, pre-B cells, and T regulatory cells, is not involved in signal transduction. The intermediate affinity form consists CD122 and CD132 heterodimer, while the high affinity form consists of an CD25, CD122 and CD132 heterotrimer. Both the intermediate and high affinity forms of the receptor are involved in receptor-mediated endocytosis and transduction of mitogenic signals from interleukin 2. IL2RB also forms one of the three subunits of the IL-15 receptor, and mainly expressed on CD4+ T cell, CD8+ T cell, Treg, NK cell, the activation of the receptor increases proliferation of CD8+ effector T cells. IL-2 has essential roles in key functions of the immune system, tolerance and immunity, primarily via its direct effects on T cells. In the thymus, where T cells mature, it prevents autoimmune diseases by promoting the differentiation of certain immature T cells into regulatory T cells, which suppress other T cells that are otherwise primed to attack normal healthy cells in the body. IL-2 also promotes the differentiation of T cells into effector T cells and into memory T cells when the initial T cell is also stimulated by an antigen, thus helping the body fight off infections. The relative clinical safety and efficacy of administering anti-CD25 radioimmunoconjugates and immunotoxins in various haematological tumour indications has been established and clinical trials of a novel CD25-directed antibody drug conjugate are underway.

Targeting strategy

The mouse Il2 gene that encoding the full coding sequence was replaced by human IL2 full coding sequence in B-hIL2/hIL2RA/hIL2RB mice.

The exons 2-6 of mouse Il2ra gene that encodes the extracellular domain were replaced by human IL2RA exons 2-6 in B-hIL2/hIL2RA/hIL2RB mice.

The exons 2~8 of mouse Cd122 gene that encodes the extracellular domain were replaced by human IL2RB exons 2-8 in B-hIL2/hIL2RA/hIL2RB mice.

Protein expression analysis

Strain specific IL2 expression analysis in homozygous B-hIL2/hIL2RA/ hIL2RB mice by ELISA. Serum was collected from wild-type mice (+/+) and homozygous B-hIL2/hIL2RA/ hIL2RB mice (H/H) stimulated with anti-mCD3 and anti-mCD28 in vitro, and analyzed by ELISA with species-specific IL2 ELISA kit. Mouse IL2 was detectable in wild-type mice. Human IL2 was exclusively detectable in homozygous B-hIL2/hIL2RA/ hIL2RB mice but not in wild-type mice.(ND: Not detectable)

Details

IL2RA protein expression in T cells

Strain specific IL2RA expression analysis in homozygous B-hIL2/hIL2RA/hIL2RB mice (H/H) by flow cytometry. Splenocytes were collected from wild-type mice (+/+) and homozygous B-hIL2/hIL2RA/hIL2RB mice (H/H) stimulated with anti-CD3ε in vivo, and analyzed by flow cytometry with anti-IL2RA antibody. Mouse IL2RA was detectable in T cells of wild-type mice. Human IL2RA was exclusively detectable in T cells of homozygous B-hIL2/hIL2RA/hIL2RB (H/H) but not in wild-type mice by the species-specific anti-IL2RA antibody.

 

IL2RA protein expression in CD4+ T cells

Strain specific IL2RA expression analysis in homozygous B-hIL2/hIL2RA/hIL2RB mice (H/H) by flow cytometry. Splenocytes were collected from wild-type mice (+/+) and homozygous B-hIL2/hIL2RA/hIL2RB mice (H/H) stimulated with anti-CD3ε in vivo, and analyzed by flow cytometry with anti-IL2RA antibody. Mouse IL2RA was detectable in CD4+ T cells of wild-type mice. Human IL2RA was exclusively detectable in CD4+ T cells of homozygous B-hIL2/hIL2RA/hIL2RB (H/H) but not in wild-type mice by the species-specific anti-IL2RA antibody.

 

IL2RA protein expression in CD8+ T cells

Strain specific IL2RA expression analysis in homozygous B-hIL2/hIL2RA/hIL2RB mice (H/H) by flow cytometry. Splenocytes were collected from wild-type mice (+/+) and homozygous B-hIL2/hIL2RA/hIL2RB mice (H/H) stimulated with anti-CD3ε in vivo, and analyzed by flow cytometry with anti-IL2RA antibody. Mouse IL2RA was detectable in CD8+ T cells of wild-type mice. Human IL2RA was exclusively detectable in CD8+ T cells of homozygous B-hIL2/hIL2RA/hIL2RB (H/H) but not in wild-type mice by the species-specific anti-IL2RA antibody.