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Severe liver degeneration and lack of NF-kappaB activation in NEMO/IKKgamma-deficient mice.

Phosphorylation of IkappaB, an inhibitor of NF-kappaB, is an important step in the activation of the transcription factor NF-kappaB. Phosphorylation is mediated by the IkappaB kinase (IKK) complex, known to contain two catalytic subunits: IKKalpha and IKKbeta. A novel, noncatalytic component of this kinase complex called NEMO (NF-kappaB essential modulator)/IKKgamma was identified recently. We have generated NEMO/IKKgamma-deficient mice by gene targeting. Mutant embryos die at E12.5-E13.0 from severe liver damage due to apoptosis. NEMO/IKKgamma-deficient primary murine embryonic fibroblasts (MEFs) lack detectable NF-kappaB DNA-binding activity in response to TNFalpha, IL-1, LPS, and Poly(IC) and do not show stimulus-dependent IkappaB kinase activity, which correlates with a lack of phosphorylation and degradation of IkappaBalpha. Consistent with these data, mutant MEFs show increased sensitivity to TNFalpha-induced apoptosis. Our data provide in vivo evidence that NEMO/IKKgamma is the first essential, noncatalytic component of the IKK complex.

Pubmed ID: 10766741


  • Rudolph D
  • Yeh WC
  • Wakeham A
  • Rudolph B
  • Nallainathan D
  • Potter J
  • Elia AJ
  • Mak TW


Genes & development

Publication Data

April 1, 2000

Associated Grants


Mesh Terms

  • Animals
  • Apoptosis
  • Cell Survival
  • Cells, Cultured
  • Embryo, Mammalian
  • Fetal Death
  • Fibroblasts
  • I-kappa B Kinase
  • Liver
  • Mice
  • Mice, Knockout
  • NF-kappa B
  • Protein-Serine-Threonine Kinases
  • Tumor Necrosis Factor-alpha