B-hPD-L1/hCD27 mice

Basic Information

Strain Name
C57BL/6-Cd274tm1(CD274) Cd27tm1(CD27)/Bcgen
Stock Number
120537
Common Name
B-hPD-L1/hCD27 mice
Source/Investigator
Bcgen (Beijing Biocytogen Co., Ltd)
Related Genes
CD27(CD27 molecule); Cd274 (CD274 antigen)
Species
C57BL/6
Appearance
Black
Genotypes
Homozygous

Description

PD-L1 (Programmed cell death ligand-1), also known as B7-H1 and CD274, is mainly expressed in antigen-presenting cells (APCs) and activated T cells, and is one of the two ligands of PD-1. The interaction between PD1 and PD-L1 plays an important role in the negative regulation of the immune response. PD-L1 is highly expressed in a variety of solid tumors. PD-1 and PD-L1 interactions can reduce T Cell Activation and promote tumor immune escape. The PD-1/PD-L1 signaling pathway can be blocked and antitumor immune response can be restored by using by anti-PD-1 or anti-PD-L1 antibodies to block the binding of PD1 to PD-L1.

CD27 is a TNF receptor super family member. It is expressed on the surface of T and B cells, and its binding with CD70 provides a co-stimulatory signal for T and B Cell Proliferation and for B cells producing immunoglobulins. Treating mice with a CD27 agonist antibody effectively enhanced the antitumor immune response for lymphoma and B16 melanoma, providing putative targets for tumor immunotherapy.

Targeting Strategy

Gene targeting strategy for B-hPD-L1/hCD27 mice .

The exon 3 of mouse Cd274 gene that encode the extracellular domain were replaced by human CD274 exon 3, The exons 1-5  of mouse Cd27 gene that  encode the extracellular domain were replaced by human CD27 exons 1-5  in B-hPD-1/hCD27 mice.

Details

Protein Expression Analysis

 

 

 

 

 

 

 

 

 

 

Strain specific PD-L1 expression analysis in homozygous B-hPD-L1/hCD27  mice by flow cytometry. Splenocytes were collected from WT and homozygous B-hPD-L1/hCD27 mice stimulated with anti-CD3ε in vivo, and analyzed by flow cytometry with species-specific anti-PD-L1 antibody. Mouse PD-L1 was exclusively detectable in WT mice. Human PD-L1 were exclusively detectable in B-hPD-L1/hCD27 but not WT mice.

Strain specific CD27 expression analysis in homozygous B-hPD-L1/hCD27  mice by flow cytometry. Splenocytes were collected from WT and homozygous B-hPD-L1/hCD27 mice stimulated with anti-CD3ε in vivo, and analyzed by flow cytometry with species-specific anti-CD27 antibody. Mouse CD27 was detectable in WT and B-hPD-L1/hCD27 mice. Human CD27 were exclusively detectable in B-hPD-L1/hCD27 but not WT mice. This might result from the cross-recognition of hCD27 by anti-mCD27 antibodies.

References

  1. Clin Cancer Res 2016; published online Nov 8. DOI:10.1158/1078-0432.CCR-16-1741
  2. Blood First Edition paper, May 11, 2010; DOI 10.1182/blood-2010-02-271874.
  3. Journal of Clinical Oncology 35, no. 18 (June 20 2017) 2028-2036. DOI: 10.1200/JCO.2016.70.1508
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