Tnfrsf1a Conditional Knockout mouse models

Tnfrsf1a, the mouse ortholog of human TNFRSF1A, encodes TNFR1 (p55), a receptor whose four cysteine-rich extracellular domains bind soluble and membrane TNF and whose cytoplasmic death domain nucleates complex I through TRADD, RIPK1, TRAF2, and cIAP1 and cIAP2, where LUBAC-generated linear ubiquitin recruits TAB and IKK complexes for NF-kB and MAPK output. When ubiquitin editing fails or translation is blocked, RIPK1 disengages into cytosolic complex II, producing caspase-8 apoptosis or RIPK3 and MLKL necroptosis, while ADAM17 shedding generates soluble receptor that buffers ligand, and human cysteine-altering mutations cause TNF receptor associated periodic syndrome through misfolding and retention. Nulls are viable and resistant to endotoxin lethality, so germline deletion is a workhorse, conditional alleles assign requirement to intestinal epithelium, endothelium, or neurons, patient point knockins model autoinflammation, and humanization is needed because etanercept and infliximab engage human ligand. Match alleles to shock, colitis, or demyelination endpoints.

A floxed Tnfrsf1a allele paired with Cre gives spatial control that whole body knockouts cannot offer. People use it to separate developmental roles from adult homeostasis, to model somatic mutations, and to match disease that begins in one organ.