B6-hCD40/hCD40LG Mouse
Product Name
B6-hCD40/hCD40LG Mouse
Product ID
C001781
Strain Name
C57BL/6NCya-Cd40tm1(hCD40)Cd40lgtm1(hCD40LG)/Cya
Backgroud
C57BL/6NCya
Status
When using this mouse strain in a publication, please cite “B6-hCD40/hCD40LG Mouse (Catalog C001781) were purchased from Cyagen.”
Product Type
Age
Genotype
Sex
Quantity
Gene Alias
p50, Bp50, CDW40, TNFRSF5, IGM, IMD3, TRAP, gp39, CD154, CD40L, HIGM1, T-BAM, TNFSF5, hCD40L
Chromosome
Chr 20, Chr X
Datasheet
Strain Description
The CD40 gene encodes CD40, a transmembrane protein belonging to the tumor necrosis factor receptor (TNFR) superfamily. Primarily expressed on antigen-presenting cells (APCs) such as B lymphocytes, macrophages, and dendritic cells, CD40 is also found on a variety of non-immune cells including endothelial cells, fibroblasts, epithelial cells, and smooth muscle cells, as well as many tumor cells [1]. The CD40LG gene is located on the X chromosome (Xq26.3) and encodes CD40 ligand (CD40L, also known as CD154), a type II transmembrane protein mainly expressed on activated T cells, platelets, and some B cells. Under inflammatory conditions, monocytes, natural killer cells, mast cells, and basophils can also be induced to express CD40L [2-4].
The interaction of CD40 with its ligand, CD40L (CD154), is a critical costimulatory signal essential for T-dependent humoral and cell-mediated immunity. This interaction triggers downstream signaling pathways, including NF-κB, JNK, and JAK/STAT, leading to B cell activation, proliferation, differentiation, isotype switching, memory B cell development, germinal center formation, and enhanced APC function and cytokine production [5]. Dysregulation of CD40/CD40L signaling pathway is implicated in the pathogenesis of numerous diseases, including autoimmune disorders like inflammatory bowel disease (IBD), type 1 diabetes (T1D), multiple sclerosis, and rheumatoid arthritis (RA), as well as cardiovascular diseases such as atherosclerosis, certain neurological conditions including Alzheimer's disease (AD) and traumatic brain injury, and various cancers [5-7].
Due to the important role of the CD40/CD40L interaction in immune activation, CD40/CD40L has been an important target for immunotherapy. In recent years, significant progress has been made in CD40/CD40L-targeted therapy. Various drugs have been developed, including agonistic/antagonistic monoclonal antibodies, cellular vaccines, adenoviral vectors, and protein antagonists, and have shown therapeutic potential in malignant tumors, autoimmune diseases, and allograft rejection [1].
The B6-hCD40/hCD40LG mouse is a dual-gene humanized model (for CD40 and CD40LG) generated by crossing B6-hCD40 mice (Catalog No.: C001721) with B6-hCD40LG mice (Catalog No.: C001720). The B6-hCD40/hCD40LG mouse model can be used for research on the mechanisms and therapeutic approaches of diseases such as autoimmune diseases, cancer, and cardiovascular diseases, as well as for the development of CD40/CD40L-targeted drugs.
Reference
Tang T, Cheng X, Truong B, Sun L, Yang X, Wang H. Molecular basis and therapeutic implications of CD40/CD40L immune checkpoint. Pharmacol Ther. 2021 Mar;219:107709.
Grewal IS, Flavell RA. CD40 and CD154 in cell-mediated immunity. Annu Rev Immunol. 1998;16:111-35.
Henn V, Slupsky JR, Gräfe M, Anagnostopoulos I, Förster R, Müller-Berghaus G, Kroczek RA. CD40 ligand on activated platelets triggers an inflammatory reaction of endothelial cells. Nature. 1998 Feb 5;391(6667):591-4.
Elgueta R, Benson MJ, de Vries VC, Wasiuk A, Guo Y, Noelle RJ. Molecular mechanism and function of CD40/CD40L engagement in the immune system. Immunol Rev. 2009 May;229(1):152-72.
Karnell JL, Rieder SA, Ettinger R, Kolbeck R. Targeting the CD40-CD40L pathway in autoimmune diseases: Humoral immunity and beyond. Adv Drug Deliv Rev. 2019 Feb 15;141:92-103.
Daub S, Lutgens E, Münzel T, Daiber A. CD40/CD40L and Related Signaling Pathways in Cardiovascular Health and Disease-The Pros and Cons for Cardioprotection. Int J Mol Sci. 2020 Nov 12;21(22):8533.
Ots HD, Tracz JA, Vinokuroff KE, Musto AE. CD40-CD40L in Neurological Disease. Int J Mol Sci. 2022 Apr 8;23(8):4115.
Strain Strategy
Figure 1. Gene editing strategy of B6-hCD40 Mice. The endogenous extracellular domain of the mouse Cd40 was replaced with the human CD40 extracellular domain. The murine signal peptide and transmembrane-cytoplasmic region were preserved.
Figure 2. Gene editing strategy of B6-hCD40LG mice. The mouse Cd40lg endogenous extracellular domain will be replaced with the human CD40LG extracellular domain. The murine transmembrane-cytoplasmic region will be preserved.
Application Area
Screening, development, and preclinical evaluation of CD40/CD40L-targeted drugs;
Research on the pathological mechanisms and therapeutic approaches of autoimmune diseases such as systemic lupus erythematosus (SLE) and lupus nephritis (LN);
Research on various malignant tumors;
Research on cardiovascular diseases and neurological diseases.
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