GATA-1 as a regulator of mast cell differentiation revealed by the phenotype of the GATA-1low mouse mutant.
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.
Migliaccio
Anna Rita
AR
Department of Biomorphology, University G. D'Annunzio, 66100 Chieti, Italy. migliar@iss.it
Rana
Rosa Alba
RA
Sanchez
Massimo
M
Lorenzini
Rodolfo
R
Centurione
Lucia
L
Bianchi
Lucia
L
Vannucchi
Alessandro Maria
AM
Migliaccio
Giovanni
G
Orkin
Stuart H
SH
D016475:3T3 Cells; D000818:Animals; D001202:Ascitic Fluid / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology / Q000502:physiology; D018920:Coculture Techniques; D003114:Colony-Forming Units Assay; D003239:Connective Tissue Cells / Q000166:cytology / Q000276:immunology; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000276:immunology / Q000502:physiology*; D004742:Enhancer Elements, Genetic; D050981:Erythroid-Specific DNA-Binding Factors; D005260:Female; D050982:GATA1 Transcription Factor; D015870:Gene Expression; D008407:Mast Cells / Q000166:cytology* / Q000276:immunology / Q000502:physiology; D051379:Mice; D008817:Mice, Mutant Strains; D011401:Promoter Regions, Genetic; D013234:Stem Cells / Q000166:cytology / Q000276:immunology / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics* / Q000276:immunology / Q000502:physiology*; D014161:Transduction, Genetic
D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; C494689:Gata1 protein, mouse; D014157:Transcription Factors