B6-hCD40LG Mouse
Product Name
B6-hCD40LG Mouse
Product ID
C001720
Strain Name
C57BL/6NCya-Cd40lgtm1(hCD40LG)/Cya
Backgroud
C57BL/6NCya
Status
When using this mouse strain in a publication, please cite “B6-hCD40LG Mouse (Catalog C001720) were purchased from Cyagen.”
Product Type
Age
Genotype
Sex
Quantity
Gene Name
CD40LG
Gene Alias
IGM, IMD3, TRAP, gp39, CD154, CD40L, HIGM1, T-BAM, TNFSF5, hCD40L
NCBI ID
Chromosome
Chr X (Human)
MGI ID
Datasheet
Strain Description
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 [1-3]. This protein binds to CD40 on the surface of antigen-presenting cells (such as B cells and dendritic cells), mediating key immune functions including T cell-dependent B cell activation, immunoglobulin class switching, and germinal center formation [3]. The CD40/CD40L interaction also regulates thrombosis, inflammatory responses, hematopoiesis, and the tumor immune microenvironment. Abnormal regulation of CD40LG is associated with X-linked hyper-IgM syndrome (XHIGM), a primary immunodeficiency disease characterized by recurrent infections due to defective antibody production [4]. In addition, abnormal expression of CD40L is involved in diseases such as systemic lupus erythematosus and atherosclerosis through its pro-inflammatory effects [5-6]. 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 [7].
The B6-hCD40LG mice are a humanized model constructed by using gene editing technology to replace the endogenous extracellular domain of the mouse Cd40lg gene with the extracellular domain of the human CD40LG gene. This model can be used for research on the disease mechanisms and treatment methods of autoimmune diseases, cardiovascular diseases, cancers, etc., as well as for CD40LG-targeted drug development.
Reference
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.
Meng X, Yang B, Suen WC. Prospects for modulating the CD40/CD40L pathway in the therapy of the hyper-IgM syndrome. Innate Immun. 2018 Jan;24(1):4-10.
Ramanujam M, Steffgen J, Visvanathan S, Mohan C, Fine JS, Putterman C. Phoenix from the flames: Rediscovering the role of the CD40-CD40L pathway in systemic lupus erythematosus and lupus nephritis. Autoimmun Rev. 2020 Nov;19(11):102668.
Lutgens E, Daemen MJ. CD40-CD40L interactions in atherosclerosis. Trends Cardiovasc Med. 2002 Jan;12(1):27-32.
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.
Strain Strategy
Figure 1. Gene editing strategy of B6-hCD40LG mice. The mouse Cd40lg endogenous extracellular domain was replaced with the human CD40LG extracellular domain. The murine transmembrane-cytoplasmic region was be preserved.
Application Area
Screening, development, and preclinical efficacy evaluation of CD40LG-targeted drugs;
Research on the pathological mechanisms and treatment methods of autoimmune diseases such as systemic lupus erythematosus (SLE) and lupus nephritis (LN);
Research on cardiovascular diseases, cancers, etc.
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