Traf6 Conditional Knockout mouse models

Encoding an essential K63-specific E3 ubiquitin ligase, Traf6 is the mouse ortholog of human TRAF6 and pairs its RING and zinc finger region with the UBC13 and UEV1A conjugating complex to build unanchored and substrate-linked K63 polyubiquitin chains that recruit TAB2 and TAB3 for TAK1 activation and NEMO for IKK activation, placing it immediately downstream of MyD88 and IRAK1 and IRAK4 for TLR and IL-1R signaling and downstream of RANK, CD40, and TGF-beta receptors. Its TRAF domain also autoubiquitinates and oligomerizes, giving threshold-like responses. Germline nulls die perinatally with severe osteopetrosis from failed osteoclast differentiation, absent lymph nodes, and neural tube defects, so conditional deletion is essential, while RING-dead or UBC13-binding knockins distinguish catalytic from scaffolding roles and are far more informative than a null for signaling questions. No paralog substitutes, so single-locus conditional genetics usually suffices. Align alleles to osteoclastogenesis, innate cytokine output, or regulatory T cell development.

A floxed Traf6 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.