Functional Redundancy of the Nuclear Factor κB Inhibitors IκBα and IκBβ

Abstract

The transcription factor NF-kappaB is sequestered in the cytoplasm by the inhibitor proteins of the IkappaB family. Each member of the IkappaB exhibits structural and biochemical similarities as well as differences. In an effort to address the functional redundancy of two closely related IkappaB molecules, IkappaBalpha and IkappaBbeta, we generated knock-in mice by replacing the IkappaBalpha gene with the IkappaBbeta gene. The knock-in mice do not express IkappaBalpha, but express a T7-tagged IkappaBbeta under the promoter and regulatory sequence of ikba. Unlike the IkappaBalpha-deficient mice, which display severe postnatal developmental defects and die by postnatal day 8, homozygous knock-in mice survive to adulthood, are fertile, and exhibit no apparent abnormalities. Furthermore, thymocytes and embryonic fibroblasts from the knock-in animals exhibit an inducible NF-kappaB response similar to that of wild-type animals. These results indicate that IkappaBalpha and IkappaBbeta share significant similarities in their biochemical activity, and that they acquired their different functions from divergent expression patterns during evolution.