B6-huCD3/huDLL3 Mouse
Product Name
B6-huCD3/huDLL3 Mouse
Product ID
C001902
Strain Name
C57BL/6NCya-Cd3tm2(hCD3)Dll3tm1(hDLL3)/Cya
Backgroud
C57BL/6NCya
Status
When using this mouse strain in a publication, please cite “B6-huCD3/huDLL3 Mouse (Catalog C001902) were purchased from Cyagen.”
Product Type
Age
Genotype
Sex
Quantity
Gene Alias
T3D, IMD19, CD3DELTA, CD3-DELTA, T3E, TCRE, IMD18, CD3epsilon, T3G, IMD17, CD3GAMMA, CD3-GAMMA, SCDO1
Chromosome
Chr 11, Chr 11, Chr 11, Chr 19
MGI ID
Datasheet
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 DLL3 (Delta-like canonical Notch ligand 3) gene encodes a transmembrane protein belonging to the Delta/Serrate/Lag-2 (DSL) family of ligands. Functioning within the highly conserved Notch signaling pathway, DLL3 exhibits a unique, inhibitory role, contrasting with the canonical activating function of other Notch ligands. It is believed to antagonize Notch signaling by preventing ligand-receptor interactions or by promoting receptor degradation, a mechanism critical for establishing proper cell fate decisions during development [4]. This is particularly evident in the formation of somites, where DLL3's function is essential for the rhythmic segmentation of the presomitic mesoderm [5]. While its expression is largely restricted to fetal tissues and progenitor cells in healthy adults, DLL3 is ectopically and highly expressed in a number of neuroendocrine tumors, including small cell lung cancer (SCLC), making it a promising therapeutic target. Pathogenic variants in the DLL3 gene are directly linked to Spondylocostal dysostosis type 1, a congenital disorder of vertebral segmentation [6].
The B6-huCD3/huDLL3 mouse is a dual-gene humanized model obtained by mating B6-huCD3 mice (catalog number: C001325) with B6-huDLL3 mice (catalog number: C001854). This model can be used for studying the pathological mechanisms and treatment methods of tumors and autoimmune diseases, as well as for the development of CD3/DLL3-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.
Furuta M, Kikuchi H, Shoji T, Takashima Y, Kikuchi E, Kikuchi J, Kinoshita I, Dosaka-Akita H, Sakakibara-Konishi J. DLL3 regulates the migration and invasion of small cell lung cancer by modulating Snail. Cancer Sci. 2019 May;110(5):1599-1608.
Ramesh PS, Chu LF. Species-specific roles of the Notch ligands, receptors, and targets orchestrating the signaling landscape of the segmentation clock. Front Cell Dev Biol. 2024 Jan 29;11:1327227.
Umair M, Younus M, Shafiq S, Nayab A, Alfadhel M. Clinical genetics of spondylocostal dysostosis: A mini review. Front Genet. 2022 Nov 25;13:996364.
Strain Strategy
Figure 1. Diagram of the gene editing strategy for the generation of B6-huCD3 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-huDLL3 mice. The mouse Dll3 endogenous extracellular domain is replaced with the human DLL3 extracellular domain. The murine signal peptide and transmembrane-cytoplasmic region are preserved.
Application Area
Research on the immune system;
Research on T cell activation and antigen recognition;
Research on immunosuppressive therapy for autoimmune diseases;
Research on the pathological mechanisms and treatment methods of malignant tumors with high DLL3 expression;
Screening, development, and pre-clinical evaluation of other CD3/DLL3-targeted drugs.
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