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B6-hCD3/hBCMA Mouse
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B6-hCD3/hBCMA Mouse
Product Name
B6-hCD3/hBCMA Mouse
Product ID
C001833
Strain Name
C57BL/6NCya-Cd3tm2(hCD3)Tnfrsf17em1(hTNFRSF17)/Cya
Backgroud
C57BL/6NCya
When using this mouse strain in a publication, please cite “B6-hCD3/hBCMA Mouse (Catalog C001833) were purchased from Cyagen.”
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Basic Information
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Basic Information
Gene Name
CD3E & CD3D & CD3G & TNFRSF17
Gene Alias
T3E, TCRE, IMD18, CD3epsilon, T3D, IMD19, CD3DELTA, CD3-DELTA, T3G, IMD17, CD3GAMMA, CD3-GAMMA, BCM, BCMA, CD269, TNFRSF13A
NCBI ID
916 & 915 & 917 & 608
Chromosome
Chr 11, Chr 11, Chr 11, Chr 16
MGI ID
MGI:88332; MGI:88331; MGI:88333; MGI:1343050
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Datasheet
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Strain Description
Cluster of differentiation 3 (CD3) is a multimeric protein complex that is essential for T cell activation and antigen recognition. It consists of five different polypeptide chains (γ, δ, ε, ζ, and η) that are noncovalently associated with the T cell receptor (TCR). The TCR is responsible for recognizing antigens presented by antigen-presenting cells (APCs), while CD3 transduces the activation signal into the T cell and activates helper T-cells and cytotoxic T-cells [1-2]. The CD3-TCR complex is expressed on the surface of all mature T cells, and its assembly is required for T cell development and function. CD3 plays a crucial role in stabilizing the TCR and facilitating its interaction with antigens. It also recruits signaling molecules to the TCR, which initiates a cascade of events that leads to T cell activation. CD3 is a highly specific T cell marker, and its expression is increased upon T cell activation. This makes it a valuable tool for identifying and characterizing T cells in tissues and blood samples. CD3 staining is also used to diagnose T-cell lymphomas and leukemias. Due to its essential role in T cell activation, CD3 is a promising target for immunosuppressive therapy. Several anti-CD3 monoclonal antibodies have been developed and are being tested in clinical trials for the treatment of autoimmune diseases, such as type 1 diabetes and rheumatoid arthritis [3].
The TNFRSF17 gene, also known as BCMA, encodes a protein belonging to the tumor necrosis factor receptor superfamily. This protein is predominantly expressed in mature B lymphocytes, particularly plasma cells, with lower expression in early B cells and non-B cells [4-5]. As a type III transmembrane glycoprotein, TNFRSF17 plays a critical role in B cell survival and differentiation, acting as a key regulator of B cell maturation [5]. Functionally, TNFRSF17 primarily acts as a receptor for the B cell-activating factor (BAFF). Upon BAFF binding, it activates both the classical NF-κB pathway and the non-classical MAPK8/JNK pathway, subsequently regulating downstream gene expression to promote B cell survival, proliferation, and antibody secretion. Furthermore, TNFRSF17 can interact with TNFR-associated factors (TRAFs) 1, 2, and 3, further mediating physiological processes related to cell differentiation and growth [4-5]. Multiple studies have demonstrated that the TNFRSF17 gene and its protein are associated with various B cell-related diseases. Notably, this gene exhibits abnormally high expression in diseases such as multiple myeloma and systemic lupus erythematosus, rendering it a potential therapeutic target for these conditions [6-7].
The B6-hCD3/hBCMA mouse is a dual-gene humanized model generated by crossing B6-hCD3 mice (Catalog No.: C001325) with B6-hBCMA (TNFRSF17) mice (Catalog No.: C001630). This model can be used for researching the pathological mechanisms and therapeutic approaches of diseases such as autoimmune diseases and multiple myeloma, as well as for the development of CD3/BCMA-targeted drugs.
Reference
Dong D, Zheng L, Lin J, Zhang B, Zhu Y, Li N, Xie S, Wang Y, Gao N, Huang Z. Structural basis of assembly of the human T cell receptor-CD3 complex. Nature. 2019 Sep;573(7775):546-552.
Dykhuizen M, Ceman J, Mitchen J, Zayas M, MacDougall A, Helgeland J, Rakasz E, Pauza CD. Importance of the CD3 marker for evaluating changes in rhesus macaque CD4/CD8 T-cell ratios. Cytometry. 2000 May 1;40(1):69-75.
Bolt S, Routledge E, Lloyd I, Chatenoud L, Pope H, Gorman SD, Clark M, Waldmann H. The generation of a humanized, non-mitogenic CD3 monoclonal antibody which retains in vitro immunosuppressive properties. Eur J Immunol. 1993 Feb;23(2):403-11.
Yu B, Jiang T, Liu D. BCMA-targeted immunotherapy for multiple myeloma. J Hematol Oncol. 2020 Sep 17;13(1):125.
Coquery CM, Erickson LD. Regulatory roles of the tumor necrosis factor receptor BCMA. Crit Rev Immunol. 2012;32(4):287–305.
Tan CR, Shah UA. Targeting BCMA in Multiple Myeloma. Curr Hematol Malig Rep. 2021 Oct;16(5):367-383.
Martin J, Cheng Q, Laurent SA, Thaler FS, Beenken AE, Meinl E, Krönke G, Hiepe F, Alexander T. B-Cell Maturation Antigen (BCMA) as a Biomarker and Potential Treatment Target in Systemic Lupus Erythematosus. Int J Mol Sci. 2024 Oct 9;25(19):10845.
Strain Strategy
Figure 1. Gene editing strategy of B6-hCD3 mice: The mouse Cd3e, Cd3d, and Cd3g genes which encode the three components of the CD3 complex, Cd3ε, Cd3δ, and Cd3γ, were replaced by the corresponding human homologous genes.
Figure 2. Gene editing strategy of B6-hBCMA (TNFRSF17) mice: The mouse Tnfrsf17 endogenous extracellular domain was replaced with the human TNFRSF17 extracellular domain.
Application Area
Screening, development, and preclinical efficacy and safety evaluation of CD3/BCMA-targeted drugs;
Research on T cell activation and antigen recognition;
Research on immunosuppressive therapies for autoimmune diseases;
Research on the pathological mechanisms and therapeutic approaches of multiple myeloma, systemic lupus erythematosus (SLE), and various B cell-related diseases.
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