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. In human T-cell leukaemias such regulators belong to diverse protein families and may normally be expressed widely (for example, Ttg-1/rbtn1, Ttg-2/rbtn2), exclusively outside the haematopoietic system (for example, Hox11), or specifically in haematopoietic cells and other selected sites (for example, tal-1/SCL, lyl-1). Aberrant expression within T cells is though to interfere with programmes of normal maturation. The most frequently activated gene in acute T-cell leukaemias, tal-1 (also called SCL), encodes a candidate regulator of haematopoietic development, a basic-helix-loop-helix protein, related to critical myogenic and neurogenic factors. Here we show by targeted gene disruption in mice 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 or the LIM protein rbtn2. 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.
Division of Hematology/Oncology, Children's Hospital, Boston, Massachusetts.
R A
RA
Shivdasani
E L
EL
Mayer
S H
SH
Orkin
D000818:Animals; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D004920:Erythropoiesis / Q000502:physiology*; D005312:Fetal Blood; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D011518:Proto-Oncogene Proteins; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D013601:T-Lymphocytes; D014157:Transcription Factors
D051792:Basic Helix-Loop-Helix Proteins; D017931:DNA Primers; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors; C489366:Tal1 protein, mouse