[HTML][HTML] Female mice heterozygous for IKKγ/NEMO deficiencies develop a dermatopathy similar to the human X-linked disorder incontinentia pigmenti

C Makris, VL Godfrey, G Krähn-Senftleben… - Molecular cell, 2000 - cell.com
C Makris, VL Godfrey, G Krähn-Senftleben, T Takahashi, JL Roberts, T Schwarz, L Feng…
Molecular cell, 2000cell.com
IKKγ/NEMO is the essential regulatory subunit of the IκB kinase (IKK), encoded by an X-
linked gene in mice and humans. It is required for NF-κB activation and resistance to TNF-
induced apoptosis. Female mice heterozygous for Ikkγ/Nemo deficiency develop a unique
dermatopathy characterized by keratinocyte hyperproliferation, skin inflammation,
hyperkeratosis, and increased apoptosis. Although Ikkγ+/− females eventually recover, Ikkγ−
males die in utero. These symptoms and inheritance pattern are very similar to those of …
Abstract
IKKγ/NEMO is the essential regulatory subunit of the IκB kinase (IKK), encoded by an X-linked gene in mice and humans. It is required for NF-κB activation and resistance to TNF-induced apoptosis. Female mice heterozygous for Ikkγ/Nemo deficiency develop a unique dermatopathy characterized by keratinocyte hyperproliferation, skin inflammation, hyperkeratosis, and increased apoptosis. Although Ikkγ+/− females eventually recover, Ikkγ males die in utero. These symptoms and inheritance pattern are very similar to those of incontinentia pigmenti (IP), a human genodermatosis, synthenic with the IKKγ/NEMO locus. Indeed, biopsies and cells from IP patients exhibit defective IKKγ/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 IKKγ/NEMO-deficient cells trigger an inflammatory reaction that eventually leads to their death.
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