Rela Knockout mouse models

Rela encodes p65, the ortholog of human RELA and the principal transactivating subunit of canonical NF-kappaB, which dimerizes with p50 through its Rel homology domain, is retained in the cytoplasm by IkappaB alpha, and enters the nucleus after IKK beta phosphorylates IkappaB alpha and triggers its ubiquitin-dependent degradation, with Ser536 and Ser276 phosphorylation and p300 acetylation tuning output at kappaB elements. Germline deletion is embryonic lethal at midgestation from TNF-driven hepatocyte apoptosis, a lethality rescued by concurrent Tnfrsf1a deficiency, which is a useful genetic maneuver but shifts the inflammatory baseline. Conditional nulls with hepatocyte, myeloid or intestinal epithelial Cre drivers are therefore standard for inflammation and tumor promotion endpoints, while phospho-site or transactivation domain knockins separate nuclear entry from cofactor recruitment. Rel and Relb do not substitute for p65 in canonical target induction, so compensation is limited and single-locus phenotypes are usually interpretable.

Rela null animals are straightforward to genotype and phenotype when survival is acceptable. They remain a standard background for pharmacology, biomarker, and rescue studies.