Female mice heterozygous for IKK gamma/NEMO deficiencies develop a dermatopathy similar to the human X-linked disorder incontinentia pigmenti.

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.
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.)
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
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)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.

Realize the full power of the drug-disease research graph!