Nfkb1 Conditional Knockout mouse models

Nfkb1, the mouse ortholog of human NFKB1, encodes p105, which is co-translationally and post-translationally processed to the p50 DNA-binding subunit; the precursor contains a Rel homology domain plus a carboxy-terminal ankyrin repeat region that functions as its own inhibitor, sequestering RelA and c-Rel until stimulus-dependent IKK phosphorylation and betaTrCP-mediated degradation of the ankyrin segment release active dimers. Because p50 lacks a transactivation domain, p50 homodimers act as repressors at kappaB sites, so the gene contributes both activating and silencing functions, and p105 additionally scaffolds Map3k8 to link NF-kB and Erk signaling. Homozygous nulls are viable with defective B cell responses, impaired isotype switching, and heightened infection susceptibility, making germline alleles tractable. A nonprocessable p105 knockin separates precursor inhibitor function from p50 output, conditional alleles restrict loss to a lineage, and humanization supports reagent matching. Rela, Relb, c-Rel, and Nfkb2 overlap at target promoters, so compound genetics is often necessary.

Conditional deletion of Nfkb1 limits the genetic change to the lineage you choose. That helps in oncology, immunology, and metabolic work where systemic loss would muddy the read. After you confirm Cre specificity, crossing to Nfkb1 floxed stock yields usable cohorts.