Limb and skin abnormalities in mice lacking IKKα

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