B6-hPD-1/hPD-L1 Mouse
Product Name
B6-hPD-1/hPD-L1 Mouse
Product ID
I001202
Strain Name
C57BL/6Cya-Pdcd1em1(hPDCD1)Cd274em1(hCD274)/Cya
Backgroud
C57BL/6Cya
Status
When using this mouse strain in a publication, please cite “B6-hPD-1/hPD-L1 Mouse (Catalog I001202) were purchased from Cyagen.”
Product Type
Age
Genotype
Sex
Quantity
Gene Name
CD274 & PDCD1
Gene Alias
B7-H, B7H1, PDL1, PD-L1, hPD-L1, PDCD1L1, PDCD1LG1, PD1, PD-1, CD279, SLEB2, hPD-1, hPD-l, hSLE1
NCBI ID
Chromosome
Chr 9 (Human), Chr 2 (Human)
MGI ID
Datasheet
Strain Description
Programmed cell death protein 1 (PDCD1/PD-1) is a member of the B7-CD28 costimulatory receptor family. It is an inhibitory receptor expressed on activated T cells and plays a role in regulating the function of effector T cells, including CD8+ T cells, and promoting the differentiation of CD4+ T cells into regulatory T cells. PD-1 is expressed in a variety of tumors and plays an important role in antitumor immunity. In addition, PD-1 is involved in the defense against autoimmune diseases and has inhibitory effects on antitumor and antimicrobial immunity [1].
Programmed cell death 1 ligand 1 (PD-L1), also known as cluster of differentiation 274 (CD274) or B7 homolog 1 (B7H1), is an immune inhibitory receptor ligand. PD-L1 is a type I transmembrane protein with immunoglobulin V-like (IgV) and C-like (IgC) structural domains and is expressed by hematopoietic and non-hematopoietic cells, including T cells, B cells, and various types of tumor cells [2]. PD-L1 can bind to the PD-1 on the surface of CD8+ T cells, inhibiting the activity of CD8+ T cells. This interaction can prevent the immune system from damaging normal tissues, but it can also be used by tumor cells to escape immune surveillance. Monoclonal antibodies that competitively bind to PD-L1 can relieve the immune function inhibition mediated by the binding of PD-1 and PD-L1. This can reactivate CD8+ T cells, triggering the human body's anti-tumor immune response [3]. Therefore, developing of antibody drugs targeting PD-1 and PD-L1 is a hot area in tumor immunotherapy [3-5].
B6-hPD-1/hPDL1 mice are PD-1 and CD274 double humanized mouse models obtained by mating PD-1 humanized mouse models with CD274 humanized mouse models. They express human PD-1 and CD274 genomic sequences under the control of mouse promoters. This model is a valuable tool for studying cancer immunotherapy. In addition, this model also provides a powerful preclinical research platform for evaluating the efficacy and mechanism of therapeutic drugs targeting PD-1 and PD-L1.
Reference
National Center for Biotechnology Information. (2024, February 1). PDCD4 programmed cell death 4 [Homo sapiens (human)] - Gene - NCBI. National Center for Biotechnology Information. https://www.ncbi.nlm.nih.gov/gene/5133
Kornepati AVR, Vadlamudi RK, Curiel TJ. Programmed death ligand 1 signals in cancer cells. Nat Rev Cancer. 2022 Mar;22(3):174-189.
Escors D, Gato-Cañas M, Zuazo M, Arasanz H, García-Granda MJ, Vera R, Kochan G. The intracellular signalosome of PD-L1 in cancer cells. Signal Transduct Target Ther. 2018 Sep 28;3:26.
Huang CY, Wang Y, Luo GY, Han F, Li YQ, Zhou ZG, Xu GL. Relationship Between PD-L1 Expression and CD8+ T-cell Immune Responses in Hepatocellular Carcinoma. J Immunother. 2017 Nov/Dec;40(9):323-333.
Zhang C, Wu S, Xue X, Li M, Qin X, Li W, Han W, Zhang Y. Anti-tumor immunotherapy by blockade of the PD-1/PD-L1 pathway with recombinant human PD-1-IgV. Cytotherapy. 2008;10(7):711-9.
Strain Strategy
① Gene editing strategy of B6-hPD-1 mice: The mouse Pdcd1 gene was edited using gene editing technology to replace the sequence encoding the extracellular domain of mouse PD-1 protein with the sequence from the human PD1 gene encoding the human PD-1 protein extracellular domain while retaining the mouse signal peptide.
② Gene editing strategy of B6-hPDL1-V(2) mice: The gene sequence encoding the extracellular domain (immunoglobulin V-like, IgV-like) of mouse PD-L1 protein was replaced with the corresponding human PD-L1 gene sequence, while the sequence encoding the signal peptide was retained.
Figure 1. Gene editing strategy of B6-hPD-1 mice.
Figure 2. Gene editing strategy of B6-hPDL1-V(2) mice.
Application Area
PD-1/PD-L1-targeted drug screening, development, and evaluation;
Research on the pathological mechanisms and therapeutic approaches of cancer immunotherapy.
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