A novel mutation in the Nfkb2 gene generates-an NF-kappa B2 "Super repressor"
Elena Tucker, Kristy O'Donnel, Martina Fuchsberger, Adrienne A Hilton, Donald Metcalft, Kylie Greig, Natalie A Sims, Julian M Quinn, Warren S Alexander, Douglas J Hilton, Benjamin T Kile, David M Tarlinton, Robyn Starr
JOURNAL OF IMMUNOLOGY | AMER ASSOC IMMUNOLOGISTS | Published : 2007
The noncanonical NF-kappaB pathway regulates the development and function of multiple organs and cell lineages. We have generated mice harboring a novel mutation in Nfkb2 that prevents the processing of the inhibitory precursor, p100, into the active subunit, p52. Mutant mice express a complex phenotype with abnormalities in a variety of tissues, and with a spectrum that is more severe than in mice carrying a targeted deletion of Nfkb2. Signaling through the noncanonical pathway is ablated due to the absence of p52, resulting in disorganized splenic architecture and disrupted B cell development. The inhibitory precursor form of NF-kappaB2 interacts with RelA, preventing activation of RelA di..View full abstract