Limb and Skin Abnormalities in Mice Lacking IKKα

Abstract

The gene encoding inhibitor of kappa B (IκB) kinase α (IKKα; also called IKK1) was disrupted by gene targeting. IKKα-deficient mice died perinatally. In IKKα-deficient fetuses, limb outgrowth was severely impaired despite unaffected skeletal development. The epidermal cells in IKKα-deficient fetuses were highly proliferative with dysregulated epidermal differentiation. In the basal layer, degradation of IκB and nuclear localization of nuclear factor kappa B (NF-κB) were not observed. Thus, IKKα is essential for NF-κB activation in the limb and skin during embryogenesis. In contrast, there was no impairment of NF-κB activation induced by either interleukin-1 or tumor necrosis factor–α in IKKα-deficient embryonic fibroblasts and thymocytes, indicating that IKKα is not essential for cytokine-induced activation of NF-κB.