huPD-1/hPD-L1/huCD19 Mouse
Product Name
huPD-1/hPD-L1/huCD19 Mouse
Product ID
C002087
Strain Name
C57BL/6J;6NCya-Pdcd1em1(hPDCD1)Cd274em1(hCD274)Cd19em3(hCD19)/Cya
Backgroud
C57BL/6J;6NCya
Status
When using this mouse strain in a publication, please cite “huPD-1/hPD-L1/huCD19 Mouse (Catalog C002087) were purchased from Cyagen.”
Product Type
Age
Genotype
Sex
Quantity
Gene Name
CD274 & PDCD1 & CD19
Gene Alias
B7-H, B7H1, PDL1, PD-L1, hPD-L1, PDCD1L1, PDCD1LG1, PD1, PD-1, CD279, SLEB2, hPD-1, hPD-l, hSLE1, B4, CVID3
NCBI ID
Chromosome
Chr 9 (Human), Chr 2 (Human), Chr 16 (Human)
MGI ID
Datasheet
Strain Description
Programmed cell death protein 1 (PDCD1/PD-1) is a member of the B7-CD28 family of costimulatory receptor proteins. It is expressed on activated T cells and functions as an immunosuppressive receptor involved 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 various tumors and plays an important role in antitumor immunity. In addition, PD-1 is involved in immune tolerance and suppresses antitumor and antimicrobial immune responses [1].
PDL1, also known as programmed cell death 1 ligand 1 (PD-L1), cluster of differentiation 274 (CD274), or B7 homolog 1 (B7-H1), encodes an immunosuppressive receptor ligand mainly expressed by hematopoietic and non-hematopoietic cells, including T cells, B cells, and various tumor cells [2]. PD-L1 is a type I transmembrane protein containing immunoglobulin V-like (IgV) and C-like (IgC) domains. PD-L1 interacts with the PD-1 receptor expressed on T cells, thereby inhibiting T cell activation and effector function. This interaction prevents excessive immune responses against normal tissues but can also be exploited by tumor cells to evade immune surveillance. Monoclonal antibodies targeting PD-L1 can disrupt the interaction between PD-1 and PD-L1, reverse PD-1/PD-L1-mediated immune suppression, reactivate T cells, and initiate antitumor immune responses [3].
The CD19 gene encodes a member of the immunoglobulin superfamily and serves as a key co-receptor in the B cell receptor (BCR) signaling pathway, playing an essential role in B cell development, activation, and differentiation. CD19 is a pan-B cell marker that is specifically expressed in the B cell lineage and remains stably expressed throughout B cell development, from pre-B cells to mature B cells and memory B cells. CD19 acts as a positive regulator of BCR signaling. The CD19 protein forms a B cell-specific signaling complex with CD21 (complement receptor type 2), CD81 (tetraspanin), and CD225 (Leu13), which lowers the threshold for antigen-induced B cell activation [4].
The huPD-1/hPD-L1/huCD19 mouse is a triple-gene humanized model generated by crossing the hPDL1-V(2) mouse (Product No.: C001235), the huPD-1 mouse (Product No.: C001524), and the huCD19 mouse (Product No.: C001731). This model can be used for pharmacodynamic evaluation, mechanism of action studies, and combination therapeutic strategy development of anti-CD19 therapeutics and PD-1/PD-L1 immune checkpoint inhibitors. It supports the evaluation of combination therapies involving anti-CD19 CAR-T cells, bispecific antibodies, and immune checkpoint inhibitors, as well as studies of B cell–T cell interactions and tumor immune microenvironment mechanisms. This model provides a preclinical research platform for developing innovative immunotherapies for B-cell malignancies, including acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL).
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.
Komura K. CD19: a promising target for systemic sclerosis. Front Immunol. 2024 Oct 3;15:1454913.
Strain Strategy
The huPD-1/hPD-L1/huCD19 mouse is a triple-gene humanized model generated by crossing the hPDL1-V(2) mouse (Catalog No.: C001235), the huPD-1 mouse (Catalog No.: C001524), and the huCD19 mouse (Catalog No.: C001731).
Figure 1. Gene editing strategy of huPD-1 mice. The mouse Pdcd1 gene was edited to replace the sequence encoding the extracellular domain of mouse PD-1 with the corresponding human PDCD1 sequence while retaining the mouse signal peptide.
Figure 2. Gene editing strategy of 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 3. Gene editing strategy of huCD19 mice. The sequences from the start codon to partial intron 4 of the mouse Cd19 gene were replaced with the sequences from the start codon to partial intron 4 of the human CD19 gene.
Application Area
Efficacy evaluation, mechanism of action research, and development of combination therapy strategies for anti-CD19 drugs and PD-1/PD-L1 immune checkpoint inhibitors;
Development of innovative immunotherapies for B-cell malignancies, such as acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL).
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