GATA-1 as a Regulator of Mast Cell Differentiation Revealed by the Phenotype of the GATA-1low Mouse Mutant

Open Access

3 February 2003

journal article
Published by Rockefeller University Press in The Journal of Experimental Medicine

Vol. 197 (3) , 281-296
https://doi.org/10.1084/jem.20021149

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 (neoΔHS 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.

Keywords

This publication has 70 references indexed in Scilit:

Development of myelofibrosis in mice genetically impaired for GATA-1 expression (GATA-1low mice)
Blood, 2002
Making Eosinophils Through Subtle Shifts in Transcription Factor Expression
The Journal of Experimental Medicine, 2002
Selective loss of gastrointestinal mast cells and impaired immunity in PI3K-deficient mice
Nature Immunology, 2002
Importance of leucine zipper domain of mitranscription factor (MITF) for differentiation of mast cells demonstrated using mice/mice mutant mice of which MITF lacks the zipper domain
Blood, 2001
Inhibitory effect of the transcription factor encoded by the mutant mi microphthalmia allele on transactivation of mouse mast cell protease 7 gene
Blood, 2001
Identification of a Committed Precursor for the Mast Cell Lineage
Science, 1996
Retroviral Gene Transfer Using Safe and Efficient Packaging Cell Lines
Annals of the New York Academy of Sciences, 1990
Megakaryocytic and erythrocytic lineages share specific transcription factors
Nature, 1990
Expression of an erythroid transcription factor in megakaryocytic and mast cell lineages
Nature, 1990
Fate of bone marrow-derived cultured mast cells after intracutaneous, intraperitoneal, and intravenous transfer into genetically mast cell-deficient W/Wv mice. Evidence that cultured mast cells can give rise to both connective tissue type and mucosal mast cells.
The Journal of Experimental Medicine, 1985