B6-hPD-1/hCTLA4 Mouse
Product Name
B6-hPD-1/hCTLA4 Mouse
Product ID
I001143
Strain Name
C57BL/6NCya-Pdcd1em1(hPDCD1)Ctla4em1(hCTLA4)/Cya
Backgroud
C57BL/6NCya
Status
When using this mouse strain in a publication, please cite “B6-hPD-1/hCTLA4 Mouse (Catalog I001143) were purchased from Cyagen.”
Product Type
Age
Genotype
Sex
Quantity
Gene Name
CTLA4 & PDCD1
Gene Alias
CD, GSE, GRD4, ALPS5, CD152, CTLA-4, IDDM12, CELIAC3, PD1, PD-1, CD279, SLEB2, hPD-1, hPD-l, hSLE1
NCBI ID
Chromosome
Chr 2 (Human), Chr 2 (Human)
MGI ID
Datasheet
Strain Description
PD-1 and CTLA-4 are checkpoint receptors that critically modulate T cell immunity. The genes PDCD1 and CTLA4 encode PD-1 and CTLA-4 respectively, with CTLA4 expression largely restricted to T cells, while PDCD1 is evident in activated T cells, B cells, and myeloid populations [1]. These transmembrane proteins function as key negative regulators of T cell activation [2]. CTLA-4 primarily operates in lymphoid tissues during early immune responses to restrain T cell proliferation, whereas PD-1 predominantly acts in peripheral tissues during the effector phase to dampen T cell activity and limit immunopathology, particularly in chronically stimulated or ‘exhausted’ T cells [2-3]. Aberrant regulation of PD-1 and CTLA-4 is implicated in the pathogenesis of cancers, including melanoma, non-small cell lung cancer, and renal cell carcinoma, as well as chronic viral infections such as hepatitis B and C [1][4]. Clinically, monoclonal antibodies targeting CTLA-4 (e.g., ipilimumab) and PD-1 (e.g., nivolumab, pembrolizumab) are established immunotherapeutic agents that enhance anti-tumor responses. By blocking these negative signaling pathways, these monoclonal antibodies restore the anti-tumor activity of T cells, significantly enhancing anti-tumor responses [1-2]. These drug applications have not only improved the treatment outcomes for various cancers but also offer new strategies for the treatment of chronic viral infections.
B6-hPD-1/hCTLA4 mouse is a dual humanized model of PD1 and CTLA4 constructed by humanizing the mouse Pdcd1 gene based on the CTLA4 humanized mouse model (Catalog No. C001413), due to the fact that the mouse Pdcd1 gene and Ctla4 gene are on the same chromosome. These mice express human CTLA4 and PDCD1 genomic sequences under the control of mouse promoters. This model is capable of reproducing the human PD-1/CTLA4 signaling pathway and is a valuable tool for studying cancers and chronic viral infections. Furthermore, this model provides a powerful preclinical research platform for evaluating the efficacy and mechanism of therapeutic drugs targeting the PD-1/CTLA4 signaling pathway.
Reference
Liu JN, Kong XS, Huang T, Wang R, Li W, Chen QF. Clinical Implications of Aberrant PD-1 and CTLA4 Expression for Cancer Immunity and Prognosis: A Pan-Cancer Study. Front Immunol. 2020 Sep 10;11:2048.
Buchbinder EI, Desai A. CTLA-4 and PD-1 Pathways: Similarities, Differences, and Implications of Their Inhibition. Am J Clin Oncol. 2016 Feb;39(1):98-106.
Cai Z, Ang X, Xu Z, Li S, Zhang J, Pei C, Zhou F. A pan-cancer study of PD-1 and CTLA-4 as therapeutic targets. Transl Cancer Res. 2021 Sep;10(9):3993-4001.
Cho H, Kang H, Lee HH, Kim CW. Programmed Cell Death 1 (PD-1) and Cytotoxic T Lymphocyte-Associated Antigen 4 (CTLA-4) in Viral Hepatitis. Int. J. Mol. Sci. 2017; 18(7):1517.
Strain Strategy
Figure 1. Gene editing strategy of 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 PDCD1 gene encoding the human PD-1 protein extracellular domain. The murine signal peptide region was remained.
Figure 2. Gene editing strategy of B6-hCTLA4 mice (Catalog No. C001413). The mouse Ctla4 gene was edited using gene editing technology to replace the sequence encoding the extracellular domain of mouse CTLA4 protein with the sequence from the human CTLA4 gene encoding the human CTLA4 protein extracellular domain while retaining the mouse signal peptide.
Application Area
PD-1/CTLA4-targeted drug screening, development, and evaluation；
Research on the pathological mechanisms and therapeutic approaches of cancers and chronic viral infections.
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