Absence of blood formation in mice lacking the T-cell leukaemia oncoprotein tal-1/SCL

CHROMOSOMAL translocations associated with malignancies often result in deregulated expression of genes encoding transcription factors 1 . In human T-cell leukaemias such regulators belong to diverse protein families and may normally be expressed widely (for example, Ttg-1/rbtnl, Ttg-2/rbtn2) 2,3 , exclusively outside the haematopoietic system (for example, Hoxll) 4 , or specifically in haematopoietic cells and other selected sites (for example, tal-1/ SCL, lyl-1) 5,6 . Aberrant expression within T cells is thought to interfere with programmes of normal maturation. The most frequently activated gene in acute T-cell leukaemias, tal-1 (also called SCL) 7,8 , encodes a candidate regulator of haematopoietic development 9 , a basic-helix-loop-helix protein 5 , related to critical myogenic 10 and neurogenic 11 factors. Here we show by targeted gene disruption in mice 12 that tal-1 is essential for embryonic blood formation in vivo . With respect to embryonic erythropoiesis, tal-1 deficiency resembles loss of the erythroid transcription factor GATA-1 13,14 or the LIM protein rbtn2 15 .Profound reduction in myeloid cells cultured in vivo from tal-1 null yolk sacs suggests a broader defect manifest at the myelo-erythroid or multipotential progenitor cell level.