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

doi:10.1084/jem.20021149

Published 3 February 2003. doi:10.1084/jem.20021149

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© Rockefeller University Press, 0022-1007/2003/2/281 $5.00
The Journal of Experimental Medicine, Volume 197, Number 3, 281-296

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

Anna Rita Migliaccio¹^,2, Rosa Alba Rana¹, Massimo Sanchez³, Rodolfo Lorenzini⁴, Lucia Centurione¹, Lucia Bianchi⁵, Alessandro Maria Vannucchi⁵, Giovanni Migliaccio¹^,3 and Stuart H. Orkin⁶

¹ Department of Biomorphology, University G. D'Annunzio, 66100 Chieti, Italy
² Laboratory of Clinical Biochemistry, Istituto Superiore di Sanità, 00161 Rome, Italy
³ Laboratory of Cell Biology, Istituto Superiore di Sanità, 00161 Rome, Italy
⁴ Laboratory of Servizio Qualità Sicurezza Animale, Istituto Superiore di Sanità, 00161 Rome, Italy
⁵ Department of Hematology, University of Florence, 50139 Florence, Italy
⁶ Department of Pediatric Oncology, Children's Hospital, Dana Farber Cancer Institute, Harvard Medical School and Howard Hughes Medical Institute, Boston, MA 02115

Address correspondence to Anna Rita Migliaccio, Clinical Biochemistry, Istituto Superiore Sanità, Viale Regina Elena 299, 00161 Rome, Italy. Phone: 39-06-4990-2690; Fax: 39-06-4938-7143; E-mail: migliar{at}iss.it

Here it is shown that the phenotype of adult mice lacking thefirst enhancer (DNA hypersensitive site I) and the distal promoterof the GATA-1 gene (neo ${Delta}$ HS or GATA-1^low mutants) reveals defectsin mast cell development. These include the presence of morphologicallyabnormal alcian blue⁺ mast cells and apoptotic metachromatic^-mast cell precursors in connective tissues and peritoneal lavageand numerous (60–70% of all the progenitors) "unique"trilineage cells committed to erythroid, megakaryocytic, andmast 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 celldifferentiation.

Key Words: mast cells • GATA-1 • differentiation • commitment • progenitor cells

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