Functional redundancy of the nuclear factor κB inhibitors IκBα and IκBβ

The transcription factor NF-kappa B is sequestered in the cytoplasm by the inhibitor proteins of the I kappa B family. Each member of the I kappa B exhibits structural and biochemical similarities as well as differences. In an effort to address the functional redundancy of two closely related I kappa B molecules, I kappa B alpha and I kappa B beta, we generated knock-in mice by replacing the I kappa B alpha gene with the I kappa B beta gene. The knock-in mice do not express I kappa B alpha, but express a T7-tagged I kappa B beta under the promoter and regulatory sequence of ikba. Unlike the I kappa B alpha-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-kappa B response similar to that of wild-type animals. These results indicate that I kappa B alpha and I kappa B beta share significant similarities in their biochemical activity, and that they acquired their different functions from divergent expression patterns during evolution.