FUNCTIONAL REDUNDANCY OF THE NUCLEAR FACTOR KAPPA-B INHIBITORS I-KAPPA-B-ALPHA AND I-KAPPA-B-BETA

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 di fferences. In an effort to address the functional redundancy of two cl osely 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 a lpha, but express a T7-tagged I kappa B beta under the promoter and re gulatory sequence of ikba. Unlike the I kappa B alpha-deficient mice, which display severe postnatal developmental defects and die by postna tal day 8, homozygous knock-in mice survive to adulthood, are fertile, and exhibit no apparent abnormalities. Furthermore, thymocytes and em bryonic fibroblasts from the knock-in animals exhibit an inducible NF- kappa B response similar to that of wild-type animals. These results i ndicate that I kappa B alpha and I kappa B beta share significant simi larities in their biochemical activity, and that they acquired their d ifferent functions from divergent expression patterns during evolution .