B6-hPD-1/hPD-L1/hVEGFA Mouse
Product Name
B6-hPD-1/hPD-L1/hVEGFA Mouse
Product ID
C001838
Strain Name
C57BL/6JCya-Pdcd1em1(hPDCD1)Cd274em1(hCD274)Vegfatm1(hVEGFA)/Cya
Backgroud
C57BL/6JCya
Status
When using this mouse strain in a publication, please cite “B6-hPD-1/hPD-L1/hVEGFA Mouse (Catalog C001838) were purchased from Cyagen.”
Product Type
Age
Genotype
Sex
Quantity
Gene Alias
PD1, PD-1, CD279, SLEB2, hPD-1, hPD-l, hSLE1, B7-H, B7H1, PDL1, PD-L1, hPD-L1, PDCD1L1, PDCD1LG1, VPF, VEGF, MVCD1
Chromosome
Chr 2, Chr 9, Chr 6
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, development of antibody drugs targeting PD-1 and PD-L1 is a hot area in tumor immunotherapy [3-5].
The Vascular Endothelial Growth Factor (VEGF) family is a group of particular endothelial growth factors intimately associated with angiogenesis. These factors promote increased vascular permeability, extracellular matrix degeneration, vascular endothelial cell migration and proliferation, and are capable of stimulating angiogenesis and increasing the permeability of existing vessels. As such, they play a pivotal role in normal vascular development and wound healing. The VEGF family comprises VEGFA, VEGFB, VEGFC, VEGFD, VEGFE, and PLGF [6]. Of these, VEGFA is the most commonly targeted in research related to neovascular ophthalmic diseases due to its crucial role in the proliferation, migration, and formation of endothelial cell microvessels [7]. Overexpression of VEGFA in the eye can result in abnormal vascular growth and leakage, leading to various ophthalmic diseases such as Age-Related Macular Degeneration (AMD), Diabetic Retinopathy (DR), and corneal neovascularization [7-8]. The progression of solid tumors depends on vascularization and angiogenesis within malignant tissues, with VEGFA playing a crucial role among various pro-angiogenic factors. The VEGFA gene is upregulated in many known tumors, correlating with tumor staging and progression. Blocking VEGFA may lead to vascular network regression, thereby inhibiting tumor growth [9]. Thus, VEGFA is an important target for anti-angiogenic cancer therapies.
B6-hPD-1/hPD-L1/hVEGFA mouse is a triple-gene humanized model generated by crossing B6-hPD-1/hPD-L1 mice (Catalog No.: I001202) with B6-hVEGFA mice (Catalog No.: C001555). This model serves as a valuable tool for research on cancer immunotherapy and can also be used for the screening, development, and preclinical evaluation of PD-1/PD-L1/VEGFA-targeted drugs.
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.
Hoeben A, Landuyt B, Highley MS, Wildiers H, Van Oosterom AT, De Bruijn EA. Vascular endothelial growth factor and angiogenesis. Pharmacol Rev. 2004 Dec;56(4):549-80.
Apte RS, Chen DS, Ferrara N. VEGF in Signaling and Disease: Beyond Discovery and Development. Cell. 2019 Mar 7;176(6):1248-1264.
Mesquita J, Castro-de-Sousa JP, Vaz-Pereira S, Neves A, Passarinha LA, Tomaz CT. Vascular endothelial growth factors and placenta growth factor in retinal vasculopathies: Current research and future perspectives. Cytokine Growth Factor Rev. 2018 Feb;39:102-115.
Chekhonin VP, Shein SA, Korchagina AA, Gurina OI. VEGF in tumor progression and targeted therapy. Curr Cancer Drug Targets. 2013 May;13(4):423-43.
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.
③ Gene editing strategy of B6-hVEGFA mice: The sequence from the CTG start codon to 3'UTR of the mouse Vegfa gene was replaced with the sequence from the CTG start codon to 3'UTR of the human VEGFA gene.
Figure 1. Gene editing strategy of B6-hPD-1 mice.
Figure 2. Gene editing strategy of B6-hPDL1-V(2) mice.
Figure 3. Gene editing strategy of B6-hVEGFA mice.
Application Area
PD-1/PD-L1/VEGFA-targeted drug screening, development, and evaluation;
Research on the tumor development and cancer immunotherapy.
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