DOMINANT INTERFERING ALLELES DEFINE A ROLE FOR C-MYB IN T-CELL DEVELOPMENT

The transcription activator c-Myb is expressed at high levels in immature thymocytes and during T-cell activation and may be a regulator of T-cell differentiation. To investigate the role of c-Myb in T-cell development, we generated transgenic mice in which two dominant interfering Myb alleles, one a competitive inhibitor of DNA binding, and the other, an active repressor comprising the Myb DNA-binding domain linked to the Drosophila Engrailed transcription repressor domain, were expressed from early times onward in T cells. Both alleles partially blocked thymopoiesis and inhibited proliferation of mature T cells. The Myb-En chimera was the more efficient repressor and might serve as an archetype for the manufacture of other dominant interfering transcription factor alleles.