Tnfrsf1a-KO Mouse

Tnfrsf1a, also known as TNFRSF1A (formerly TNFR1), encodes the 55 kDa TNF receptor. It is involved in inflammatory processes and is crucial for the regulation of the immune response, as TNF-α binding to this receptor activates various downstream signaling pathways [1].

Mutations in TNFRSF1A can cause TNF-receptor-associated periodic syndrome (TRAPS), presenting with prolonged fever and severe localized inflammation. These mutations often affect the first two cysteine-rich extracellular subdomains of the receptor, potentially impairing the cleavage of the TNFRSF1A ectodomain upon cellular activation, reducing the shedding of the soluble receptor which may act as an antagonist [1]. In multiple myeloma, TNFRSF1A overexpression leads to carfilzomib resistance by suppressing the expression of MHC genes and cell adhesion molecules, dampening antitumor immunity, while its silencing reverses resistance [2]. In osteosarcoma, TNFRSF1A was screened as a prognostic signature from necroptosis-related genes, with lower expression associated with a worse prognosis and changes in immune cell infiltration [3].

In conclusion, Tnfrsf1a is essential for normal immune-inflammatory regulation. Its mutations are linked to autoinflammatory syndromes like TRAPS. In cancer, it plays a role in drug resistance and prognosis, highlighting its importance in understanding disease mechanisms. Studies on Tnfrsf1a contribute to the understanding of immune-mediated diseases and cancer-related processes. [1,2,3]

References:

1. Galon, J, Aksentijevich, I, McDermott, M F, O'Shea, J J, Kastner, D L. . TNFRSF1A mutations and autoinflammatory syndromes. In Current opinion in immunology, 12, 479-86. doi:. https://pubmed.ncbi.nlm.nih.gov/10899034/

2. Zhao, Jie, Yang, Xuantao, Zhang, Haixi, Gu, Xuezhong. 2023. Identification of TNFRSF1A as a novel regulator of carfilzomib resistance in multiple myeloma. In Oncology research, 32, 325-337. doi:10.32604/or.2023.030770. https://pubmed.ncbi.nlm.nih.gov/38186567/

3. Zhang, Yuke, Liu, Kai, Wang, Jianzhong. . Identification of TNFRSF1A as a potential biomarker for osteosarcoma. In Cancer biomarkers : section A of Disease markers, 39, 299-312. doi:10.3233/CBM-230086. https://pubmed.ncbi.nlm.nih.gov/38250759/