The transcription factor c-Myb is expressed throughout T cell development in the thymus. However, little is understood about c-Myb function because of the embryonic lethality of traditional Myb-null mutations. Using tissue-specific deletion to abrogate c-Myb expression at distinct stages of T cell development, we identify three points at which c-Myb activity is required for normal T cell differentiation: transition through the double-negative 3 stage, survival of preselection CD4+CD8+ thymocytes, and differentiation of CD4 thymocytes. Thus, c-Myb is essential at several stages during T cell development in the thymus.
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The authors thank A. Roth (University of Cologne, Cologne, Germany) for doing the blastocyst injections; C. Goettlinger (University of Cologne) and J. Lannigan (University of Virginia, Charlottesville, Virginia) for help with cell sorting; and M. McDuffie, V. Engelhard, U. Lorenz and K. Ravichandran for critical review of the manuscript. Supported by National Institutes of Health (CA85842 to T.P.B.), Fogarty International Center (TW02297 to T.P.B.), Deutsche Forschungsgemeinschaft (SFB 243 to K.R.) and the European Union (BIO4-CT96-0077 to K.R.).
The authors declare no competing financial interests.
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Bender, T., Kremer, C., Kraus, M. et al. Critical functions for c-Myb at three checkpoints during thymocyte development. Nat Immunol 5, 721–729 (2004) doi:10.1038/ni1085
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