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J. Exp. Med.,
Volume 188, Number 6, September 21, 1998 1055-1062
B Inhibitors
IB
and IB
By
From the * Department of Oncology and the The transcription factor NF- Department of Experimental Pathology, Bristol-Myers
Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543-4000
B is sequestered in the cytoplasm by the inhibitor proteins of the
IB family. Each member of the IB exhibits structural and biochemical similarities as well as
differences. In an effort to address the functional redundancy of two closely related IB molecules, IB
and IB
, we generated knock-in mice by replacing the IB gene with the IB
gene. The knock-in mice do not express IB, but express a T7-tagged IB under the promoter and regulatory sequence of ikba. Unlike the IB-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-B response similar
to that of wild-type animals. These results indicate that IB and IB share significant similarities in their biochemical activity, and that they acquired their different functions from divergent expression patterns during evolution.
B;
IB;
transgenic mice;
knockout mice;
hematopoiesis
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