title: Complete lack of NF-kappaB activity in IKK1 and IKK2 double-deficient mice: additional defect in neurulation.
abstract: NF-kappaB activity is induced by cytokines, stress, and pathogens. IKK1 and IKK2 are critical IkappaB kinases in NF-kappaB activation. In this study mice lacking IKK1 and IKK2 died at E12. Additional defect in neurulation associated with enhanced apoptosis in the neuroepithelium was also observed. MEF cells from IKK1(-/-)/IKK2(-/-) embryos did not respond to NF-kappaB inducers. Upon crossing with kappaB-lacZ transgenic mice, double-deficient embryos also lost lacZ transgene expression in vascular endothelial cells during development. Our data suggest that IKK1 and IKK2 are essential for NF-kappaB activation in vivo and have an important role in protecting neurons against excessive apoptosis during development.
authors.affiliation: Laboratory of Genetics, The Salk Institute, La Jolla, California 92037, USA.
authors.forename: Q
authors.initials: Q
authors.lastname: Li
authors.forename: G
authors.initials: G
authors.lastname: Estepa
authors.forename: S
authors.initials: S
authors.lastname: Memet
authors.forename: A
authors.initials: A
authors.lastname: Israel
authors.forename: I M
authors.initials: IM
authors.lastname: Verma
mesh_terms: D000483:Alleles; D000818:Animals; D017209:Apoptosis; D015152:Blotting, Northern; D015153:Blotting, Western; D002467:Cell Nucleus / Q000378:metabolism; D004622:Embryo, Mammalian / Q000378:metabolism / Q000473:pathology; D004730:Endothelium, Vascular / Q000378:metabolism; D004789:Enzyme Activation; D004848:Epithelium / Q000473:pathology; D051550:I-kappa B Kinase; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D051379:Mice; D008822:Mice, Transgenic; D016296:Mutagenesis; D016328:NF-kappa B / Q000378:metabolism*; D009420:Nervous System / Q000196:embryology*; D009474:Neurons / Q000473:pathology; D010641:Phenotype; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011233:Precipitin Tests; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology*
chemical_list: D016328:NF-kappa B; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D017346:Protein Serine-Threonine Kinases; C496564:Chuk protein, mouse; D051550:I-kappa B Kinase; C496562:Ikbkb protein, mouse; C496566:Ikbke protein, mouse