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

The transcription activator c-Myb is expressed at high levels in immat ure 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 dev elopment, we generated transgenic mice in which two dominant interferi ng Myb alleles, one a competitive inhibitor of DNA binding, and the ot her, an active repressor comprising the Myb DNA-binding domain linked to the Drosophila Engrailed transcription repressor domain, were expre ssed from early times onward in T cells. Both alleles partially blocke d thymopoiesis and inhibited proliferation of mature T cells. The Myb- En chimera was the more efficient repressor and might serve as an arch etype for the manufacture of other dominant interfering transcription factor alleles.