Abstract
IKB 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 IKBα and IKBβ 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.
Original language | English (US) |
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Pages (from-to) | 1322-1328 |
Number of pages | 7 |
Journal | Genes and Development |
Volume | 13 |
Issue number | 10 |
DOIs | |
State | Published - May 15 1999 |
Externally published | Yes |
Keywords
- IKK1
- Limb
- Mice
- NF-κB
- Skeleton
- Skin
ASJC Scopus subject areas
- Genetics
- Developmental Biology