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

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