| c-Myc is the most extensively characterized member of the myc family of nuclear proto-oncogenes. c-Myc is associated with cell growth and cycling in many tissues and its deregulated expression is causally implicated in cancer, particularly lymphomagenesis. However, understanding the contribution of c-myc to the development and function of any particular cell type is confounded by the embryonic lethality of c-myc null mice. During T cell development, thymocytes successively require signals from defined surface receptors, including the IL-7 receptor, the pre-TCR, and the TCR. Activation through these receptors promotes one or more of several outcomes, including selective cell survival, cell growth and proliferation, and cell differentiation. c-Myc is expressed during all stages of T cell differentiation and is implicated in processes required for successful completion of T cell development programs.; To investigate the requirement for c-myc in T cell development, we have utilized the technique of RAG l−/− blastocyst complementation to examine the developmental potential of embryonic stem cells deficient in c-myc. Our analyses of c-myc−/− :: RAG1−/− chimerae indicate that c-myc is absolutely required for normal thymocyte development. c-Myc−/− cells are inefficient, in an age dependent manner, at populating the thymus, and subsequent thymocyte maturation is ineffective; c-myc null thymocytes fail to grow and proliferate normally at the late double-negative (DN) CD4− CD8− stage of development. 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 expression. |
