Mice hemizygous for TgN(LCK-NFKBIA)5Dwb transgene exhibit a complete inactivation of the NFKB signalling pathway. The T cell lineage expresses a trans-dominant form of IkBa that constitutively represses the activity of multiple NFKB/Rel proteins. Transgenic cells expressing this inhibitor exhibit a significant proliferative defect. Mitogenic stimulation of splenocytes leads to increased apoptosis of transgenic T cells. Transgene expression also impairs the development of normal T cell populations as evidenced by diminished numbers of TCR<sup>hi</sup>CD8 single-positive thymocytes. This defect is significantly amplified in the periphery and is accompanied by a decrease in CD4<sup>+</sup> T cells.

These I&kappa;B&alpha;(&Delta;N) mice express a transgene containing an amino acid-truncated human NFKBIA gene fused to a FLAG epitope and exhibit a significant proliferative defect and impairment of normal T cell development.

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