B6-hBAFF(TNFSF13B) Mice

Catalog Number: C001621

Strain Name: C57BL/6NCya-Tnfsf13bem1(hTNFSF13B)/Cya
Genetic Background: C57BL/6NCya

Reproduction: Homozygote x Homozygote

 

Strain Description

The TNFSF13B gene encodes B cell-activating factor (BAFF), a critical cytokine for B cell survival and maturation, primarily expressed by monocytes, macrophages, dendritic cells, and T cells [1]. BAFF, a member of the tumour necrosis factor (TNF) superfamily, functions through binding to receptors on B cells, including BAFF-R, TACI, and BCMA. Activation of these receptors initiates the NF-κB and MAPK signaling cascades, leading to B cell survival, proliferation, and immunoglobulin production [1-2]. This cytokine is essential for humoral immunity and the development of lymphoid tissues [1]. Aberrant BAFF expression and signaling are implicated in the pathogenesis of autoimmune diseases, such as systemic lupus erythematosus (SLE) and rheumatoid arthritis. BAFF overexpression can drive B cell hyperactivity and the production of autoantibodies, contributing to these conditions [2-3]. Clinically, monoclonal antibodies targeting BAFF, such as belimumab, are employed in the treatment of SLE [4]. In the tumor microenvironment, BAFF exhibits a complex role, supporting B cell lymphomas and influencing the immune response to solid tumours, exhibiting context-dependent pro- and anti-tumourigenic effects [5]. This multifaceted role highlights BAFF as a key therapeutic target in autoimmune diseases and specific B cell malignancies [1-5]. 

The B6-hBAFF(TNFSF13B) mouse is a humanized model generated using gene editing technology, in which the protein-coding sequence (CDS) encoding the extracellular domain of the human TNFSF13B protein is integrated into a specific site within the mouse Tnfsf13b gene, while retaining the endogenous gene sequence encoding the mouse cytoplasmic and transmembrane domains (aa.1-68). Homozygous B6-hBAFF(TNFSF13B) mice are viable and fertile. This model can be used for studying the pathological mechanisms and therapeutic approaches of autoimmune diseases and specific B cell malignancies and for the development of BAFF-targeted drugs.

 

Strain Strategy


Figure 1. Gene editing strategy of B6-hBAFF(TNFSF13B) mice. The region from aa.69 in exon 1 to partial intron 1 of mouse Tnfsf13b was replaced with "Human TNFSF13B CDS of extracellular domain (aa.68~285)-WPRE-BGH pA" cassette. The murine cytoplasmic and transmembrane domain (aa.1-68) were preserved.

 

Application

  • BAFF-targeted drug screening, development, and evaluation;
  • Research on the pathological mechanisms and therapeutic approaches of autoimmune diseases and specific B cell malignancies.

 

References
[1]Smulski CR, Eibel H. BAFF and BAFF-Receptor in B Cell Selection and Survival. Front Immunol. 2018 Oct 8;9:2285.
[2]Huang T, Pi C, Xu X, Feng Y, Zhang J, Gu H, Fang J. Effect of BAFF blockade on the B cell receptor repertoire and transcriptome in a mouse model of systemic lupus erythematosus. Front Immunol. 2024 Jan 9;14:1307392.
[3]Giordano D, Kuley R, Draves KE, Elkon KB, Giltiay NV, Clark EA. B cell-activating factor (BAFF) from dendritic cells, monocytes and neutrophils is required for B cell maturation and autoantibody production in SLE-like autoimmune disease. Front Immunol. 2023 Feb 27;14:1050528.
[4]Ramsköld D, Parodis I, Lakshmikanth T, Sippl N, Khademi M, Chen Y, Zickert A, Mikeš J, Achour A, Amara K, Piehl F, Brodin P, Gunnarsson I, Malmström V. B cell alterations during BAFF inhibition with belimumab in SLE. EBioMedicine. 2019 Feb;40:517-527.
[5]Ullah MA, Mackay F. The BAFF-APRIL System in Cancer. Cancers. 2023; 15(6):1791.