Functional Redundancy of the Nuclear Factor k B Inhibitors

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