Transcription factor GATA-3 is required for development of the T-cell lineage

Nature. 1996 Dec 5;384(6608):474-8. doi: 10.1038/384474a0.


THE zinc-finger transcription factor GATA-3 is expressed in haematopoietic cells and in the developing kidney and nervous system. Within the haematopoietic lineages, expression of GATA-3 is restricted to thymocytes and T cells. Functionally important GATA-3 binding sites have been identified in multiple T-cell-specific genes. Mice containing homozygous null mutations of the GATA-3 gene die on embryonic day 12, precluding a detailed assessment of the role of GATA-3 in haematopoietic development. Here we have used murine embryonic stem (ES) cells containing homozygous mutations in the GATA-3 gene (GATA-3(-/-)) in conjunction with the RAG-2(-/-) (ref. 10) and C57BL/6 complementation systems to study the role of GATA-3 in mammalian haematopoiesis. Our results show that GATA-3(-/-) ES cells can contribute to the development of the mature erythroid, myelomonocytic and B-cell lineages, but fail to give rise to thymocytes or mature peripheral T cells. The differentiation of GATA-3(-/-) T cells is blocked at or before the earliest double-negative (CD4-/CD8-) stage of thymocyte development, such that the GATA-3(-/-) ES cells are unable to contribute measurably to the double-negative thymocyte population. These findings suggest that GATA-3 is an essential and specific regulator of early thymocyte development.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blastocyst
  • Bone Marrow Cells
  • Cell Differentiation / genetics
  • Cell Differentiation / physiology
  • Cell Line
  • Cell Lineage
  • Chimera
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology*
  • Flow Cytometry
  • GATA3 Transcription Factor
  • Hematopoiesis / genetics
  • Hematopoiesis / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Proteins / genetics
  • Sequence Deletion
  • Spleen / cytology
  • T-Lymphocytes / cytology*
  • Thymus Gland / cytology
  • Trans-Activators / genetics
  • Trans-Activators / physiology*
  • Zinc Fingers*


  • DNA-Binding Proteins
  • GATA3 Transcription Factor
  • Gata3 protein, mouse
  • Proteins
  • Rag2 protein, mouse
  • Trans-Activators
  • V(D)J recombination activating protein 2