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An HMG-box-containing T-cell factor required for thymocyte differentiation

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Abstract

Two candidate genes for controlling thymocyte differentiation,T-cellfactor-1 (Tcf-1) and lymphoid enhancer-binding factor (Lef-1), encode closely related DNA-binding HMG-box proteins1,2. Their expression pattern is complex and largely overlapping during embryogenesis, yet restricted to lymphocytes postnatally3. Here we generate two independent germline mutations in Tcf-1 and find that thymocyte development in (otherwise normal) mutant mice is blocked at the transition from the CD8+, immature single-positive to the CD4+/CD8+ double-positive stage. In contrast to wild-type mice, most of the immature single-positive cells in the mutants are not in the cell cycle and the number of immunocompetent T cells in peripheral lymphoid organs is reduced. We conclude that Tcf-1 controls an essential step in thymocyte differentiation.

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Author notes

  1. Hans Clevers: To whom correspondence should be addressed

Authors and Affiliations

  1. Department of Immunology, University Hospital, PO Box 85500, 3508 GA, Utrecht, The Netherlands

    Sjef Verbeek, Frans Hofhuis, Marc van de Watering, Mariette Oosterwegel & Hans Clevers

  2. Division of Immunology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands

    David Izon & Mariette Oosterwegel

  3. Division of Molecular Genetics, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands

    Els Robanus-Maandag & Hein te Riele

  4. Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, 1066, Epalinges, Switzerland

    Anne Wilson & H. Robson MacDonald

Authors
  1. Sjef Verbeek
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  2. David Izon
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  3. Frans Hofhuis
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  4. Els Robanus-Maandag
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  5. Hein te Riele
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  6. Marc van de Watering
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  7. Mariette Oosterwegel
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  8. Anne Wilson
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  9. H. Robson MacDonald
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  10. Hans Clevers
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Verbeek, S., Izon, D., Hofhuis, F. et al. An HMG-box-containing T-cell factor required for thymocyte differentiation. Nature 374, 70–74 (1995). https://doi.org/10.1038/374070a0

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  • DOI: https://doi.org/10.1038/374070a0

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