NEMO/IKK Gamma-Deficient Mice Model Incontinentia Pigmenti

Mol Cell. 2000 Jun;5(6):981-92. doi: 10.1016/s1097-2765(00)80263-4.

Abstract

Disruption of the X-linked gene encoding NF-kappa B essential modulator (NEMO) produces male embryonic lethality, completely blocks NF-kappa B activation by proinflammatory cytokines, and interferes with the generation and/or persistence of lymphocytes. Heterozygous female mice develop patchy skin lesions with massive granulocyte infiltration and hyperproliferation and increased apoptosis of keratinocytes. Diseased animals present severe growth retardation and early mortality. Surviving mice recover almost completely, presumably through clearing the skin of NEMO-deficient keratinocytes. Male lethality and strikingly similar skin lesions in heterozygous females are hallmarks 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Cell Division
  • Cells, Cultured
  • Chemotaxis, Leukocyte
  • Cytokines / metabolism
  • Cytokines / pharmacology
  • Disease Models, Animal
  • Female
  • Gene Targeting
  • Heterozygote
  • Humans
  • Hyperpigmentation
  • I-kappa B Kinase
  • Incontinentia Pigmenti / embryology
  • Incontinentia Pigmenti / enzymology
  • Incontinentia Pigmenti / genetics*
  • Incontinentia Pigmenti / pathology
  • Keratinocytes / enzymology
  • Keratinocytes / pathology
  • Liver / embryology
  • Liver / pathology
  • Male
  • Melanins / metabolism
  • Mice
  • Mice, Knockout
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Nitric Oxide Synthase / genetics
  • Nitric Oxide Synthase / metabolism
  • Nitric Oxide Synthase Type II
  • Protein-Serine-Threonine Kinases / deficiency
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / physiology*
  • Skin / embryology
  • Skin / enzymology
  • Skin / metabolism
  • Skin / pathology
  • Up-Regulation

Substances

  • Cytokines
  • Melanins
  • NF-kappa B
  • NOS2 protein, human
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • 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