Nature Immunology
2, 307 - 315 (2001)
doi:10.1038/86308
Defining the specific physiological requirements for c-Myc in T cell developmentNataki C. Douglas1, Harris Jacobs2, Alfred L. M. Bothwell3
& Adrian C. Hayday1, 3, 41
Department of Molecular Cell and Developmental Biology, Yale University, New Haven, CT 06520, USA. 2
Department of Pediatrics, Yale University, New Haven, CT 06520, USA. 3
Section of Immunobiology, Yale University, New Haven, CT 06520, USA. 4
Peter Gorer Department of Immunobiology, Guy's King's St Thomas' Medical School, Guy's Hospital, London SE1 9RT, UK.
Correspondence should be addressed to Adrian C. Hayday adrian.hayday@kcl.ac.ukc-Myc is associated with cell growth and cycling in many tissues and its deregulated expression is causally implicated in cancer, particularly lymphomagenesis. However, the contribution of c-Myc to lymphocyte development is unresolved. We show here that the formation of normal lymphocytes by c-Myc-/- cells is selectively defective. c-Myc-/- cells are inefficient, in an age-dependent manner, at populating the thymus, and subsequent thymocyte maturation is ineffective: they fail to grow and proliferate normally at the late double-negative (DN) CD4-CD8- stage. Because N-Myc expression in thymocytes usually declines at the late DN stage, these results confirm that the nonredundant contributions of Myc family members to development are related to their distinct patterns of developmental gene expression.
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