B-hCTLA4/h4-1BB mice

Basic Information

Strain Name
C57BL/6-Ctla4tm1(CTLA4) Tnfrsf9tm1(TNFRSF9)/Bcgen
Stock Number
120539
Common Name
B-hCTLA4/h4-1BB mice
Source/Investigator
Bcgen (Beijing Biocytogen Co., Ltd)
Related Genes
CTLA4 (Cytotoxic T-lymphocyte-associated protein 4, CD152) TNFRSF9 (Tumor necrosis factor receptor superfamily, member 9)
Species
C57BL/6
Appearance
Black
Genotypes
Homozygous

Description

CTLA4 (cytotoxic T-lymphocyte-associated protein 4), also known as CD152, competitively binds to B7-1 (CD80) and B7-2 (CD86) on Antigen-Presenting Cells (APCs) to block the T cell activating signal by B7 and CD28 (on T cells) interaction. The inhibition of CTLA4 by its inhibitory antibodies enhances T cell activity. The CTLA4 antibody is the first FDA-approved antibody to treat advanced melanoma.

TNFRSF9 (Tumor necrosis factor receptor super family, member 9), also called CD137 and 4-1BB, is a co-stimulatory molecule and is mainly expressed on the surface of T, NK and mononuclear cells. CD137 is activated by its ligand CD137L or activating anti-CD137 antibodies, resulting in T Cell Activation, proliferation and cytokine production. CD137L is expressed on antigen presenting cells such as dendritic cells and macrophages and activated B cells. In vivo studies show that CD137 activation increases anti-tumor immune responses, providing a new target for immunotherapy.

Targeting Strategy

Gene targeting strategy for B-hCTLA4/h4-1BB mice.

The exon 2 of mouse Ctla4 gene that encode the IgV domain were replaced by human CTLA4 exon 2 in B-hCTLA4/h4-1BB mice. The exons 2-7 of mouse 4-1BB gene that encode the extracellular domain were replaced by human 4-1BB exons 2-7 in B-hCTLA4/h4-1BB mice.

Details

Phenotype

Protein Expression Analysis

Strain specific 4-1BB expression analysis in homozygous B-hCTLA4/h4-1BB mice by flow cytometry. Splenocytes were collected from WT and homozygous B-hCTLA4/h4-1BB (H/H) mice stimulated with anti-CD3ε in vivo, and analyzed by flow cytometry with species-specific anti-h4-1BB antibody. Mouse 4-1BB was detectable in WT mice but not homozygous B-hCTLA4/h4-1BB mice. Human 4-1BB was exclusively detectable in homozygous B-hCTLA4/h4-1BB mice but not WT mice.

Strain specific CTLA4 expression analysis in homozygous B-hCTLA4/h4-1BB mice by flow cytometry. Splenocytes were collected from WT and homozygous B-hCTLA4/h4-1BB (H/H) mice stimulated with anti-CD3ε in vivo, and analyzed by flow cytometry with species-specific anti-hCTLA4 antibody. Mouse CTLA4 was detectable in WT mice but not homozygous B-hCTLA4/h4-1BB mice. Human CTLA4 was exclusively detectable in homozygous B-hCTLA4/h4-1BB mice but not WT mice.

References

  1. J Immunol.1991 Aug 1;147(3):1037-44.
  2. J Exp Med.1991 Sep 1;174(3):561-9.
  3. PLoS One. 2014 Jan 21;9(1): e86337.
  4. Cancer Gene Ther. 2004 Mar;11(3):215-26.
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