Rescue of erythroid development in gene targeted GATA–1− mouse embryonic stem cells
Nature GeneticsPublished 1 May 1992
M. Celeste Simon, Larysa Pevny, Michael V. Wiles, Gordon Keller, Frank Costantini, Stuart H. Orkin
Citations253
SJR quartileQ1
SJR score16.59
SNIP6.64
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TL;DR
In vitro differentiation of GATA–1− mouse embryonic stem cells is used to reveal a requirement for GATA-1 during primitive (yolk sac–derived) erythropoiesis and to establish a rescue assay, showing that the block to development includes primitive, as well as definitive, erythroid cells and is complete at the level of globin RNA expression.
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.
Keywords
MedicineBiochemistry, Genetics and Molecular Biology
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