B-hPD-1/hPD-L1/h4-1BB mice

Basic Information

Strain name
C57BL/6-Pdcd1tm1(PDCD1) Cd274tm1(CD274) Tnfrsf9tm1(TNFRSF9)/Bcgen
Common name
B-hPD-1/hPD-L1/h4-1BB mice
Background
C57BL/6
Catalog number
130569
Related genes
  PD-1(Programmed death-1) ; TNFRSF9(TNF receptor superfamily member 9, also known as 4-1BB)

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 protein expression is detected in many human tumor tissues. PD-L1 expression in tumor cells could be induced by the microenvironment of tumor cells. PD-L1 expression is favorable for tumorigenesis and growth, for induction of anti-tumor T Cell apoptosis, and for escaping responses by the immune system. Inhibition of PD-1 binding to its ligand can result in tumor cells that are exposed to the killing version of the immune system, and thus is a target for cancer treatments.

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.

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-hPD-1/hPD-L1/h4-1BB mice. The exon 2 of mouse PD-1 gene that encode the IgV domain were replaced by human PD-1 exon 2 in B-hPD-1/hPD-L1/h4-1BB mice. The exon 3 of mouse Pd-l1 gene that encode the IgV domain were replaced by human PD-L1 exon 3 in B-hPD-L1/hPD-L1/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-hPD-1/hPD-L1/h4-1BBmice.

Details

Protein expression analysis

Strain specific PD-1 expression analysis in homozygous B-hPD-1/hPD-L1/h4-1BB mice by flow cytometry. Splenocytes were collected from WT and homozygous B-hPD-1/hPD-L1/h4-1BB (H/H) mice stimulated with anti-CD3ε in vivo, and analyzed by flow cytometry with species-specific anti-hPD-1 antibody. Mouse PD-1 was detectable in WT mice but not homozygous B-hPD-1/hPD-L1/h4-1BB mice. Human PD-1 was exclusively detectable in homozygous B-hPD-1/hPD-L1/h4-1BB mice but not WT mice.

 

Strain specific PD-L1 expression analysis in homozygous B-hPD-1/hPD-L1/h4-1BB mice by flow cytometry. Splenocytes were collected from WT and homozygous B-hPD-1/hPD-L1/h4-1BB (H/H) mice stimulated with anti-CD3ε in vivo, and analyzed by flow cytometry with species-specific anti-hPD-L1 antibody. Mouse PD-L1 was detectable in WT mice but not homozygous B-hPD-1/hPD-L1/h4-1BB mice. Human PD-L1 was exclusively detectable in homozygous B-hPD-1/hPD-L1/h4-1BB mice but not WT mice.

 

Strain specific 4-1BB expression analysis in homozygous B-hPD-1/hPD-L1/h4-1BB mice by flow cytometry. Splenocytes were collected from WT and homozygous B-hPD-1/hPD-L1/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-hPD-1/hPD-L1/h4-1BB mice. Human 4-1BB was exclusively detectable in homozygous B-hPD-1/hPD-L1/h4-1BB mice but not WT mice.

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