Basic Information

Strain Name
C57BL/6-CTLA4tm1(CTLA4)Bcgen/Bcgen
Stock Number
110011
Common Name
B-hCTLA4 Mice
Source/Investigator
Bcgen (Beijing Biocytogen Co., Ltd)
Related Genes
Ctla4 (cytotoxic T-lymphocyte-associated protein 4)
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.

Targeting Strategy

B-hCTLA4-Mice-targeting-strategy

Details

Phenotype

mRNA Expression Analysis

B-hCTLA4-Mice-mrna-expression-analysis

RT-PCR analysis of CTLA4 gene. The hCTLA4, but not mCTLA4, mRNA was detected in splenocytes of the homozygous B-hCTLA4 mice.

 

Protein Expression Analysis

Splenocytes from both wild type (WT)C57BL/6 and homozygous B-hCTLA-4 mice were analyzed by flow cytometry for the expression of CTLA4. Mouse CTLA4+ T cells were detectable in the WT mice, while human CTLA4+ T cells were detectable in the homozygous B-hCTLA4 mice.

 

Application

CTLA4 (Yervoy) mAb efficacy evaluation using murine colon
cancer MC38 cells

B-hCTLA4-Mice-CTLA4-yervoy-mab-efficacy-evaluation

Murine colon cancer MC38 cells were subcutaneously implanted into homozygous B-hCTLA4 mice. Mice were divided into control and treatment groups (n=5) when the tumor size was approximately 100 mm3. Three doses of the anti-hCTLA4 antibody Yervoy differentially inhibited tumor growth in the homozygous B-hCTLA4 mice, suggesting that B-hCTLA4 mouse model is an effective tool for in vivo hCTLA4 antibody efficacy studies. The average ± SEM of tumor sizes are shown in the figure. (A) Tumor average volume ± SEM, (B) Mice average weight ± SEM

References

1. Cell Research (2018) 0:1–15; doi: 10.1038/s41422-018-0012-z
2. Blood.2005;106:3127-3133
3. Scientific Reports volume7, 42913 (2017) doi: 10.1038/srep42913

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