These c-IAP2H570A mice contain the amino acid mutation H570A in exon 9 of the baculoviral IAP repeat-containing 2 (Birc3) gene. C-IAP2 (Cellular Inhibitor of Apoptosis 2) acts as an E3 ubiquitin-protein ligase which regulates non-canonical NF-kappa-B signaling, caspase activity, apoptosis, inflammatory signaling and immunity, mitogenic kinase signaling, cell proliferation, cell invasion, and metastasis. This H570A mutation is in the RING domain, inactivating the E3 ubiquitin-protein ligase activity. c-IAP2H570A protein levels are increased due to lack of autoubiquitination and degradation and exert a dominant negative effect on c-IAP1 E3 activity. As a result, c-IAP2H570A cells have constitutively active non-canonical NF-kappa-B resulting in high levels of p52 at rest. c-IAP2H570A mice have enlarged gut associated lymphoid tissue (GALT), marginal zone B cell hyperplasia, increased B cell survival, and T cell-costimulation independence.
