Embryonic lethality, liver degeneration, and impaired NF-κB activation in IKK-β-deficient mice

I kappa B kinase-alpha and -beta (IKK-alpha and IKK-beta), the catalytic subunits of the IKK complex, phosphorylate I kappa B proteins on specific serine residues, thus targeting I kappa B for degradation and activating the transcription factor NF-kappa B. To elucidate the in vivo function of IKK-beta, we generated IKK-beta-deficient mice. The homozygous mouse embryo dies at similar to 14.5 days of gestation due to liver degeneration and apoptosis. IKK-beta-deficient embryonic fibroblasts have both reduced basal NF-kappa B activity and impaired cytokine-induced NF-kappa B activation. Similarly, basal and cytokine-inducible kinase activities of the IKK complex are greatly reduced in IKK-beta-deficient cells. These results indicate that IKK-beta is crucial for liver development and regulation of NF-kappa B activity and that IKK-alpha can only partially compensate for the loss of IKK-beta.