Embryonic lethality, liver degeneration, and impaired NF-kappa B activation in IKK-beta-deficient mice

I kappa B kinase-alpha and -beta (IKK-alpha and IKK-beta), the catalytic su bunits of the IKK complex, phosphorylate I kappa B proteins on specific ser ine residues, thus targeting I kappa B for degradation and activating the t ranscription factor NF-kappa B. To elucidate the in vivo function of IKK-be ta, we generated IKK-beta-deficient mice. The homozygous mouse embryo dies at similar to 14.5 days of gestation due to liver degeneration and apoptosi s. IKK-beta-deficient embryonic fibroblasts have both reduced basal NF-kapp a B activity and impaired cytokine-induced NF-kappa B activation. Similarly , basal and cytokine-inducible kinase activities of the IKK complex are gre atly reduced in IKK-beta-deficient cells. These results indicate that IKK-b eta 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.