Abstract
Development of definitive (fetal liver–derived) red cells is blocked by a targeted mutation in the gene encoding the transcription factor GATA–1. We used in vitro differentiation of GATA–1− mouse embryonic stem (ES) cells to reveal a requirement for GATA–1 during primitive (yolk sac–derived) erythropoiesis and to establish a rescue assay. We show that the block to development includes primitive, as well as definitive, erythroid cells and is complete at the level of globin RNA expression; that the introduction of a normal GATA–1 gene restores developmental potential both in vivo and in vitro; and that efficient rescue is dependent on a putative autoregulatory GATA–motif in the distal promoter. Use of in vitro differentiated ES cells bridges a gap between conventional approaches to gene function in cell lines and analysis of loss of function mutations in the whole animal.
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Simon, M., Pevny, L., Wiles, M. et al. Rescue of erythroid development in gene targeted GATA–1− mouse embryonic stem cells. Nat Genet 1, 92–98 (1992). https://doi.org/10.1038/ng0592-92
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DOI: https://doi.org/10.1038/ng0592-92