IKK1-deficient mice exhibit abnormal development of skin and skeleton
Copyright policy )IKK1-deficient mice exhibit abnormal development of skin and skeleton
IkappaB kinases (IKKs) IKK1 and IKK2 are two putative IkappaBalpha kinases involved in NF-kappaB activation. To examine the in vivo functions of IKK1, we generated IKK1-deficient mice. The mutant mice are perinatally lethal and exhibit a wide range of developmental defects. Newborn mutant mice have shiny, taut, and sticky skin without whiskers. Histological analysis shows thicker epidermis, which is unable to differentiate. Limbs and tail are wrapped inside the skin and do not extend properly out of the body trunk. Skeleton staining reveals a cleft secondary palate, split sternebra 6, and deformed incisors. NF-kappaB activation mediated by TNFalpha and IL-1 is diminished in IKK1-deficient mouse embryonic fibroblast (MEF) cells. The IKK complex in the absence of IKK1 is capable of phosphorylating IkappaBalpha and IkappaBbeta in vitro. Our results support a role for IKK1 in NF-kappaB activation and uncover its involvement in skin and skeleton development. We conclude further that the two related kinases IKK1 and IKK2 have distinct functions and can not be substituted for each other's functions.
- Salk Institute for Biological Studies United States
Time Factors, Interleukin-6, Tumor Necrosis Factor-alpha, NF-kappa B, Mice, Transgenic, Protein Serine-Threonine Kinases, Embryo, Mammalian, Bone and Bones, I-kappa B Kinase, Mice, Inbred C57BL, Mice, Phenotype, Mutagenesis, Skin Abnormalities, Animals, Epidermis, Interleukin-1
Time Factors, Interleukin-6, Tumor Necrosis Factor-alpha, NF-kappa B, Mice, Transgenic, Protein Serine-Threonine Kinases, Embryo, Mammalian, Bone and Bones, I-kappa B Kinase, Mice, Inbred C57BL, Mice, Phenotype, Mutagenesis, Skin Abnormalities, Animals, Epidermis, Interleukin-1
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