Abstract |
IKK gamma/NEMO is the essential regulatory subunit of the I kappa B kinase (IKK), encoded by an X-linked gene in mice and humans. It is required for NF-kappa B activation and resistance to TNF-induced apoptosis. Female mice heterozygous for Ikk gamma/Nemo deficiency develop a unique dermatopathy characterized by keratinocyte hyperproliferation, skin inflammation, hyperkeratosis, and increased apoptosis. Although Ikk gamma+/- females eventually recover, Ikk gamma- males die in utero. These symptoms and inheritance pattern are very similar to those of incontinentia pigmenti (IP), a human genodermatosis, synthenic with the IKK gamma/NEMO locus. Indeed, biopsies and cells from IP patients exhibit defective IKK gamma/NEMO expression but normal expression of IKK catalytic subunits. This unique self-limiting disease, the first to be genetically linked to the IKK signaling pathway, is dependent on X-chromosome inactivation. We propose that the IKK gamma/NEMO-deficient cells trigger an inflammatory reaction that eventually leads to their death.
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Authors | C Makris, V L Godfrey, G Krähn-Senftleben, T Takahashi, J L Roberts, T Schwarz, L Feng, R S Johnson, M Karin |
Journal | Molecular cell
(Mol Cell)
Vol. 5
Issue 6
Pg. 969-79
(Jun 2000)
ISSN: 1097-2765 [Print] United States |
PMID | 10911991
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Chemokines
- Protein Serine-Threonine Kinases
- CHUK protein, human
- Chuk protein, mouse
- I-kappa B Kinase
- IKBKB protein, human
- IKBKE protein, human
- Ikbkb protein, mouse
- Ikbke protein, mouse
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Topics |
- Animals
- Apoptosis
- Cell Division
- Cell Line
- Chemokines
(genetics)
- Disease Models, Animal
- Dosage Compensation, Genetic
- Female
- Fetal Death
- Gene Targeting
- Heterozygote
- Humans
- I-kappa B Kinase
- Incontinentia Pigmenti
(genetics, pathology)
- Inflammation
(genetics, pathology)
- Liver
(pathology)
- Male
- Mice
- Mice, Knockout
- Protein Serine-Threonine Kinases
(deficiency, genetics, physiology)
- Signal Transduction
- Skin
(metabolism, pathology)
- Spleen
(pathology)
- Thymus Gland
(pathology)
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