B6-h4-1BB(TNFRSF9) Mice

Catalog Number: C001604

Strain Name: C57BL/6NCya-Tnfrsf9^{em1(hTNFRSF9)}/Cya

Genetic Background: C57BL/6NCya

Reproduction: Homozygote x Homozygote

Strain Description

The TNFRSF9 gene, also known as 4-1BB/CD137, encodes a protein that belongs to the TNF receptor superfamily. This receptor aids in the clonal expansion, survival, and development of T cells. It can also induce the proliferation of peripheral monocytes, enhance TCR/CD3-triggered activation-induced T cell apoptosis, and regulate CD28 co-stimulation to promote Th1 cell responses. TRAF adaptor proteins can bind to it and transmit signals that activate NF-kappaB. Many immune cell types express TNFRSF9, including activated NK cells, NKT cells, B cells, eosinophils, basophils, mast cells, neutrophils, mature Tregs, activated monocytes, and dendritic cells. Additionally, TNFRSF9 may be expressed in non-immune cell types such as endothelial cells, neurons, astrocytes, and microglia. TNFRSF9 plays roles in innate and adaptive immunity, including cancer immunology and autoimmune diseases ^[1]. Due to its broad expression profile and immune response functions, 4-1BB is a potential target for cancer and immunotherapy. In recent years, research on second-generation 4-1BB agonists has been expanding, with various strategies being implemented to overcome the liver toxicity and efficacy limitations of the first generation ^[2-3].

The B6-h4-1BB(TNFRSF9) mouse is a humanized model. The sequence encoding the endogenous extracellular domain of the mouse Tnfrsf9 is replaced in situ with the sequence encoding the human TNFRSF9 extracellular domain. This model can be used for studies on cancer immunology and autoimmune diseases, as well as for the development, screening, and evaluation of 4-1BB agonists in preclinical research.

Strain Strategy

Figure 1. Gene editing strategy of B6-h4-1BB(TNFRSF9) mice. The mouse Tnfrsf9 endogenous extracellular domain (aa.24~187) was replaced with the human TNFRSF9 extracellular domain (aa.24~186).

Application

• Research on cancer immunotherapy and autoimmune diseases;
• Preclinical studies on the development, screening, and evaluation of 4-1BB agonists.

References
[1]Eckstrum K, Bany BM. Tumor necrosis factor receptor subfamily 9 (Tnfrsf9) gene is expressed in distinct cell populations in mouse uterus and conceptus during implantation period of pregnancy. Cell Tissue Res. 2011 Jun;344(3):567-76.
[2]Kim AMJ, Nemeth MR, Lim SO. 4-1BB: A promising target for cancer immunotherapy. Front Oncol. 2022 Sep 14;12:968360.
[3]Claus C, Ferrara-Koller C, Klein C. The emerging landscape of novel 4-1BB (CD137) agonistic drugs for cancer immunotherapy. MAbs. 2023 Jan-Dec;15(1):2167189.