IKK1-deficient mice exhibit abnormal development of skin and skeleton
Open Access
- 15 May 1999
- journal article
- Published by Cold Spring Harbor Laboratory in Genes & Development
- Vol. 13 (10) , 1322-1328
- https://doi.org/10.1101/gad.13.10.1322
Abstract
IκB kinases (IKKs) IKK1 and IKK2 are two putative IκBα kinases involved in NF-κB 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-κB activation mediated by TNFα 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 IκBα and IκBβ in vitro. Our results support a role for IKK1 in NF-κB 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.Keywords
This publication has 30 references indexed in Scilit:
- Role of Rel/NF-κB transcription factors during the outgrowth of the vertebrate limbNature, 1998
- Inhibition of NF-κB activity results in disruption of the apical ectodermal ridge and aberrant limb morphogenesisNature, 1998
- Targeted expression of activated erbB-2 to the epidermis of transgenic mice elicits striking developmental abnormalities in the epidermis and hair follicles.1998
- Alterations in NF-κB function in transgenic epithelial tissue demonstrate a growth inhibitory role for NF-κBProceedings of the National Academy of Sciences, 1998
- Defective stratum corneum and early neonatal death in mice lacking the gene for transglutaminase 1 (keratinocyte transglutaminase)Proceedings of the National Academy of Sciences, 1998
- Requirement for NF-κB in osteoclast and B-cell developmentGenes & Development, 1997
- Osteopetrosis in mice lacking NF-κB1 and NF-κB2Nature Medicine, 1997
- IκB Kinase-β: NF-κB Activation and Complex Formation with IκB Kinase-α and NIKScience, 1997
- The IκB Kinase Complex (IKK) Contains Two Kinase Subunits, IKKα and IKKβ, Necessary for IκB Phosphorylation and NF-κB ActivationPublished by Elsevier ,1997
- Genetic approaches to study Rel/NF-κB/IκB function in miceSeminars in Cancer Biology, 1997