Nature Genetics
1, 92 - 98 (1992)
doi:10.1038/ng0592-92
Rescue of erythroid development in gene targeted GATA−1- mouse embryonic stem cellsM. Celeste Simon1, Larysa Pevny2, Michael V. Wiles3, Gordon Keller4, Frank Costantini2
& Stuart H. Orkin1, 5
1Division of Hematology-Oncology, Children's Hospital and the Dana Farber Cancer Institute, Department of Pediatrics, Harvard Medical School, Boston, Masachusetts 02115, USA
2Department of Genetics and Development, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA
3Basel Institute for Immmunology, Postfach, CH4005, Switzerland
4National Jewish Center for Immunology, Denver, Colorado 80206, USA
5Howard Hughes Medical Institute 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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