TNFR2 is a member of the tumor necrosis factor receptor superfamily, which also contains TNFRSF1A. This protein and TNF-receptor 1 form a heterocomplex that mediates the recruitment of two anti-apoptotic proteins, c-IAP1 and c-IAP2, which possess E3 ubiquitin ligase activity. The function of IAPs in TNF-receptor signaling is unknown, however, c-IAP1 is thought to potentiate TNF-induced apoptosis by the ubiquitination and degradation of TNF-receptor-associated factor 2 (TRAF2), which mediates anti-apoptotic signals. TNFR1 encodes a member of the TNF receptor superfamily of proteins. The encoded receptor is found in membrane-bound and soluble forms that interact with membrane-bound and soluble forms, respectively, of its ligand, tumor necrosis factor alpha. Binding of membrane-bound tumor necrosis factor alpha to the membrane-bound receptor induces receptor trimerization and activation, which plays a role in cell survival, apoptosis, and inflammation. Proteolytic processing of the encoded receptor results in release of the soluble form of the receptor, which can interact with free tumor necrosis factor alpha to inhibit inflammation. Mutations in this gene underlie tumor necrosis factor receptor-associated periodic syndrome (TRAPS), characterized by fever, abdominal pain and other features. Mutations in this gene may also be associated with multiple sclerosis in human patients.
mRNA expression analysis
Strain specific analysis of TNFR1 and TNFR2 gene expression in WT and B-hTNFR2/TNFR1 mice by RT-PCR. Mouse Tnfr1 and Tnfr2 mRNA were detectable only in splenocytes of wild-type (+/+) mice. Human TNFR1 and TNFR2 mRNA were detectable only in H/H, but not in +/+ mice.
Protein expression analysis
Strain specific TNFR2 expression analysis in homozygous B-hTNFR2/hTNFR1 mice by flow cytometry. Splenocytes were collected from WT and homozygous B-hTNFR2/hTNFR1 (H/H) mice stimulated with anti-CD3ε in vivo, and analyzed by flow cytometry with species-specific anti-TNFR2 antibody. Mouse TNFR2 was detectable in WT mice. Human TNFR2 was exclusively detectable in homozygous B-hTNFR2/hTNFR1 but not WT mice.
Protein expression analysis-granulocytes
Strain specific TNFR1 expression analysis in homozygous B-hTNFR2/hTNFR1 mice by flow cytometry. Splenocytes and blood were collected from WT and homozygous B-hTNFR2/hTNFR1 (H/H) mice, and analyzed by flow cytometry with species-specific anti-TNFR1 antibody. Mouse TNFR1 was detectable in the WT mice. Human TNFR1 was exclusively detectable in homozygous B-hTNFR2/hTNFR1 but not WT mice.