Abstract
Here it is shown that the phenotype of adult mice lacking the first enhancer (DNA hypersensitive site I) and the distal promoter of the GATA-1 gene (neo Delta HS or GATA-1(low) mutants) reveals defects in mast cell development. These include the presence of morphologically abnormal alcian blue(+) mast cells and apoptotic metachromatic(-) mast cell precursors in connective tissues and peritoneal lavage and numerous (60-70% of all the progenitors) "unique" trilineage cells committed to erythroid, megakaryocytic, and mast pathways in the bone marrow and spleen. These abnormalities, which were mirrored by impaired mast differentiation in vitro, were reversed by retroviral-mediated expression of GATA-1 cDNA. These data indicate an essential role for GATA-1 in mast cell differentiation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3T3 Cells
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Animals
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Ascitic Fluid / cytology
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Ascitic Fluid / immunology
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Cell Differentiation / genetics
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Cell Differentiation / immunology
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Cell Differentiation / physiology
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Coculture Techniques
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Colony-Forming Units Assay
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Connective Tissue Cells / cytology
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Connective Tissue Cells / immunology
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DNA-Binding Proteins / genetics*
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DNA-Binding Proteins / immunology
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DNA-Binding Proteins / physiology*
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Enhancer Elements, Genetic
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Erythroid-Specific DNA-Binding Factors
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Female
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GATA1 Transcription Factor
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Gene Expression
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Mast Cells / cytology*
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Mast Cells / immunology
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Mast Cells / physiology
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Mice
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Mice, Mutant Strains
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Promoter Regions, Genetic
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Stem Cells / cytology
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Stem Cells / immunology
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Stem Cells / physiology
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Transcription Factors / genetics*
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Transcription Factors / immunology
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Transcription Factors / physiology*
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Transduction, Genetic
Substances
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DNA-Binding Proteins
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Erythroid-Specific DNA-Binding Factors
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GATA1 Transcription Factor
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Gata1 protein, mouse
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Transcription Factors