B-hPD-1/hPD-L1/hCTLA4 mice

Basic Information

Strain Name
C57BL/6-Pdcd1tm1(PDCD1) Cd274tm1(CD274)Ctla4tm1(CTLA4)/Bcgen
Common Name
B-hPD-1/hPD-L1/hCTLA4 mice
Background
C57BL/6
Catalog Number
130571
Related Genes
PD-1 (Programmed death-1); CD274 (CD274 antigen); CTLA4  (Cytotoxic T-lymphocyte-associated protein 4, CD152)

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-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. 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

Gene targeting strategy for B-hPD-1/hPD-L1/hCTLA4 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/hCTLA4 mice. The exon 3 of mouse Pd-l1 gene that encodes the extracellular domain was replaced by human PD-L1 exon 3 in B-hPD-1/hPD-L1/hCTLA4 mice. The exon 2 of mouse Ctla4 gene that encodes the extracellular domain was replaced by human CTLA4 exon 2 in B-hPD-1/hPD-L1/hCTLA4 mice.

Details

Protein expression analysis

Strain specific PD-1, PD-L1 and CTLA4 expression analysis in homozygous B-hPD-1/hPD-L1/hCTLA4 mice by flow cytometry. Splenocytes were collected from WT and homozygous B-hPD-1/hPD-L1/hCTLA4 (H/H) mice, and analyzed by flow cytometry with species-specific anti-PD-1, anti-PD-L1 and anti-CTLA4 antibody. Mouse PD-1, PD-L1 and CTLA4 were detectable in WT mice. Human PD-1, PD-L1 and CTLA4 were exclusively detectable in homozygous B-hPD-1/hPD-L1/hCTLA4 but not WT mice.

Strain specific PD-1, PD-L1 and CTLA4 expression analysis in homozygous B-hPD-1/hPD-L1/hCTLA4 mice by flow cytometry. Splenocytes were collected from WT and homozygous B-hPD-1/hPD-L1/hCTLA4 (H/H) mice stimulated with anti-CD3ε in vivo, and analyzed by flow cytometry with species-specific anti-PD-1, anti-PD-L1 and anti-CTLA4 antibody. Mouse PD-1, PD-L1 and CTLA4 were detectable in WT mice. Human PD-1, PD-L1 and CTLA4 were exclusively detectable in homozygous B-hPD-1/hPD-L1/hCTLA4 but not WT mice.

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