B-hCTLA4/hTIM3 mce

Basic Information

Strain Name
C57BL/6-Ctla4 tm1(CTLA4) Havcr2 tm1(HAVCR2) /Bcgen
Stock Number
120530
Common Name
B-hCTLA4/hTIM3 mice
Source/Investigator
Bcgen (Beijing Biocytogen Co., Ltd)
Related Genes
Ctla4 (cytotoxic T-lymphocyte-associated protein 4); Havcr2 (hepatitis A virus cellular receptor 2)
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. T-cell immunoglobulin domain and mucin domain-3 (TIM3) is an activation-induced inhibitory molecule involved in immune tolerance and T-cell exhaustion in chronic viral infection and cancers.

TIM3 maturation and cell surface expression is facilitated by forming a heterodimeric interaction with CD66a. Co-blockade of CD66a and TIM3 enhanced anti-tumor immune responses, and eliminated tumors in mouse colorectal cancer models.

Targeting Strategy

Detail

Protein expression analysis

Strain specific TIM3 expression analysis in homozygous B-hCTLA4/hTIM3 mice by flow cytometry.

Splenocytes were collected from WT and homozygous B-hCTLA4/hTIM3 (H/H) mice stimulated with anti-CD3ε in vivo, and analyzed by flow cytometry with species-specific anti-TIM3 antibody. Mouse TIM3 was detectable in WT mice. Human TIM3 was exclusively detectable in homozygous B-hCTLA4/hTIM3 but not WT mice.

Strain specific CTLA4 expression analysis in homozygous B-hCTLA4/hTIM3 mice by flow cytometry.

Splenocytes were collected from WT and homozygous B-hCTLA4/hTIM3 (H/H) mice stimulated with anti-CD3ε in vivo, and analyzed by flow cytometry with species-specific anti-CTLA4 antibody. Mouse CTLA4 was detectable in WT mice. Human CTLA4 was exclusively detectable in homozygous B-hCTLA4/hTIM3 but not WT mice.

References

  1. Cell Research (2018) 0:1–15; doi: 10.1038/s41422-018-0012-z
  2. Cancer Immunity (22 January 2013) Vol. 13, p. 5
  3. Journal of Immunological Methods. 18 November 2016. Doi: 10.1016/j.jim.2017.04.006
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