NEMO/IKK gamma-deficient mice model incontinentia pigmenti

Disruption of the X-linked gene encoding NF-kappa B essential modulator (NE MO) produces male embryonic lethality, completely blocks NF-kappa B activat ion by proinflammatory cytokines, and interferes with the generation and/or persistence of lymphocytes. Heterozygous female mice develop patchy skin l esions with massive granulocyte infiltration and hyperproliferation and inc reased apoptosis of keratinocytes. Diseased animals present severe growth r etardation and early mortality. Surviving mice recover almost completely, p resumably through clearing the skin of NEMO-deficient keratinocytes. Mate l ethality and strikingly similar skin lesions in heterozygous females are ha llmarks of the human genetic disorder incontinentia pigmenti (IP). Together with the recent discovery that mutations in the human NEMO gene cause IP, our results indicate that we have created a mouse model for that disease.