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B-hPD-1/hPD-L1/hOX40 mice
Strain Name C57BL/6-Pdcd1tm1(PDCD1)Cd274tm1(CD274)Tnfrsf4tm1(TNFRSF4)/Bcgen Common Name  B-hPD-1/hPD-L1/hOX40 mice
Background C57BL/6 Catalog number  311112
Related Genes 

PD-1(Programmed death-1) 

CD274 (CD274 antigen)

TNFRSF4(Tumor necrosis factor receptor superfamily, member 4, also known as OX40

Gene description


PD-1 (Programmed death-1) is mainly expressed on the surface of T cells and primary B cells. The two PD-1 ligands, PD-L1 and PD-L2, are widely expressed on antigen-presenting cells (APCs). PD-1 interacts with its ligands and plays an important role in the negative regulation of the immune response. 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. OX40, also known as Tnfrsf4 (Tumor necrosis factor receptor super family, member 4), is mainly expressed on the surface of activated CD4+ and CD8+ T cells, and its binding with the OX40 ligand can stimulate CD8+ T Cell Activation. The coactivation of OX40/OX40L enhances T cell function, including cytokine production, proliferation and T cell survival. An OX40 agonist can reduce Regulatory T cells (Tregs) and improve anti-tumor activity.


Targeting strategy


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Gene targeting strategy for B-hPD-1/hPD-L1/hOX40 mice. 

The exon 2 of mouse PD-1 gene that encodes the extracellular domain was replaced by human PD-1 exon 2 in B-hPD-1/hPD-L1/hOX40 mice. The exon 3 of mouse pdl1 gene that encode the extracellular domain was replaced by human PD-L1 exon 3 in B-hPD-1/hPD-L1/hOX40 mice. The exons 1-5 of mouse Tnfrsf4 gene that  encode the extracellular domain were replaced by human TNFRSF4  exons 1-5 in B-hPD-1/hPD-L1/hOX40 mice . 


Protein expression analysis


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Strain specific PD-1, PD-L1 and OX40 expression analysis in homozygous B-hPD-1/hPD-L1/hOX40 mice by flow cytometry. 

Splenocytes were collected from WT and homozygous B-hPD-1/hPD-L1/hOX40 (H/H) mice analyzed by flow cytometry with species-specific anti-PD-1 antibody, anti-PD-L1 antibody and anti-OX40 antibody. Mouse PD-1, PD-L1 and OX40 were detectable in WT mice. Human PD-1, PD-L1 and OX40 were exclusively detectable in homozygous B-hPD-1/hPD-L1/hOX40 but not WT mice. 


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Strain specific PD-1, PD-L1 and OX40 expression analysis in homozygous B-hPD-1/hPD-L1/hOX40 mice by flow cytometry.

Splenocytes were collected from WT and homozygous B-hPD-1/hPD-L1/hOX40 (H/H) mice mice after stimulation with anti-CD3ε in vivo (7.5 μg/mice) and analyzed by flow cytometry with species-specific anti-PD-1 antibody, anti-PD-L1 antibody and anti-OX40 antibody. Mouse PD-1, PD-L1 and OX40 were detectable in WT mice. Human PD-1, PD-L1 and OX40 were exclusively detectable in homozygous B-hPD-1/hPD-L1/hOX40 but not WT mice.