Limb and Skin Abnormalities in Mice Lacking IKK[small alpha, Greek]

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Abstract

The gene encoding inhibitor of kappa B (I kappa B) kinase [small alpha, Greek] (IKK[small alpha, Greek]; also called IKK1) was disrupted by gene targeting.IKK[small alpha, Greek]-deficient mice died perinatally. In IKK[small alpha, Greek]-deficient fetuses, limb outgrowth was severely impaired despite unaffected skeletal development. The epidermal cells in IKK[small alpha, Greek]-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[small alpha, Greek] 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-[small alpha, Greek] in IKK[small alpha, Greek]-deficient embryonic fibroblasts and thymocytes, indicating that IKK[small alpha, Greek] is not essential for cytokine-induced activation of NF-kappa B.

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