AN HMG-BOX-CONTAINING T-CELL FACTOR REQUIRED FOR THYMOCYTE DIFFERENTIATION

Two candidate genes for controlling thymocyte differentiation, T-cell factor-1 (Tcf-1) and lymphoid enhancer-binding factor (Lef-1), encode closely related DNA-binding HMG-box proteins(1,2). Their expression pa ttern is complex and largely overlapping during embryogenesis, yet res tricted to lymphocytes postnatally(3). Here we generate two independen t germline mutations in Tcf-1 and find that thymocyte development is ( otherwise normal) mutant mice is blocked at the transition from the CD 8(+), immature single-positive to the CD4(+)/CD8(+) double-positive st age. Is contrast to wild-type mice, most of the immature single-positi ve cells in the mutants are not in the cell cycle and the number of im munocompetent T cells in peripheral lymphoid organs is reduced. We con clude that Tcf-1 controls an essential step in thymocyte differentiati on.