Ikbkb Conditional Knockout mouse models

Ikbkb, the mouse ortholog of human IKBKB, encodes IKK2, the dominant catalytic subunit of the IkB kinase complex, which also contains Chuk-encoded IKK1 and the Ikbkg scaffold; once Tak1 phosphorylates the activation loop at Ser177 and Ser181, IKK2 phosphorylates IkBalpha on Ser32 and Ser36, triggering betaTrCP-dependent ubiquitination and proteasomal destruction and freeing RelA and p50 dimers for nuclear entry. Homozygous deletion causes mid-gestation lethality from TNF-driven hepatocyte apoptosis, which can be rescued on a Tnfr1-deficient background but otherwise mandates conditional alleles, so lineage-restricted deletion with LysM-Cre, Cd19-Cre, or Villin-Cre is the practical route for inflammation and tumor studies. A constitutively active Ser177 and Ser181 to glutamate knockin asks whether canonical NF-kB output alone drives a phenotype, a kinase-dead allele distinguishes catalysis from complex assembly, and humanization supports selective inhibitor pharmacology. Chuk partially compensates, so pair compound alleles with a driver validated in the target compartment.

Tissue restricted knockout of Ikbkb keeps wild type function everywhere else. Breeding is often more robust, and the setup mirrors patient biology where mutations arise in a subset of cells.