Severe liver degeneration in mice lacking the I kappa B kinase 2 gene

Phosphorylation of inhibitor of kappa B (I kappa B) proteins is an importan t step in the activation of the transcription nuclear factor kappa B (NF-ka ppa B) and requires two I kappa B kinases, IKK1 (IKK alpha) and IKK2 (IKK b eta). Mice that are devoid of the IKK2 gene had extensive Liver damage from apoptosis and died as embryos, but these mice could be rescued by the inac tivation of the gene encoding tumor necrosis factor receptor 1. Mouse embry onic fibroblast cells that were isolated from IKK2(-/-) embryos showed a ma rked reduction in tumor necrosis factor-alpha (TNF-alpha)- and interleukin- 1 alpha-induced NF-kappa B activity and an enhanced apoptosis in response t o TNF-alpha. IKK1 associated with NF-kappa B essential modulator (IKK gamma /IKKAP1), another component of the IKK complex. These results show that IKK 2 is essential for mouse development and cannot be substituted with IKK1.