Defining the specific physiological requirements for c-Myc in T cell development

c-Myc is associated with cell growth and cycling in many tissues and its de regulated expression is causally implicated in cancer, particularly lymphom agenesis. However, the contribution of c-Myc to lymphocyte development is u nresolved. 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 m aturation 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 tha t the nonredundant contributions of Myc family members to development are r elated to their distinct patterns of developmental gene expression.