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Vol. 13, No. 10, pp. 1322-1328, May 15, 1999
The Salk Institute, La Jolla, California 92037 USA
I
B kinases (IKKs) IKK1 and IKK2 are two putative IB
kinases
involved in NF-B 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-B activation mediated by TNF 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 IB and
IB
in vitro. Our results support a role for IKK1 in NF-B
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.
[Key Words:
IKK1; NF-B; skin; skeleton; limb; mice]
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