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

Abstract

THE zinc-finger transcription factor GATA-3 is expressed in haematopoietic cells and in the developing kidney and nervous system1–7. 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 genes1,6–8. 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 development9. 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 ery-throid, 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.

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Ting, CN., Olson, M., Barton, K. et al. Transcription factor GATA-3 is required for development of the T-cell lineage. Nature 384, 474–478 (1996). https://doi.org/10.1038/384474a0

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