The zinc-finger proto-oncogene Gfi-1b is essential for development of the erythroid and megakaryocytic lineages (original) (raw)

1. Shireen Saleque1,
2. Scott Cameron1,2,3, and
3. Stuart H. Orkin1,4
4. 1Department of Pediatric Oncology, Children's Hospital, Dana Farber Cancer Institute, Harvard Medical School, and Howard Hughes Medical Institute, Boston, Massachusetts 02115, USA;2Department of Biology, Massachusetts Institute of Technology, and Howard Hughes Medical Institute, Cambridge Massachusetts 02139, USA

Abstract

Gfi-1 and Gfi-1b are novel proto-oncogenes identified by retroviral insertional mutagenesis. By gene targeting, we establish that Gfi-1b is required for the development of two related blood lineages, erythroid and megakaryocytic, in mice.Gfi-1b −/− embryonic stem cells fail to contribute to red cells of adult chimeras. Gfi-1b −/− embryos exhibit delayed maturation of primitive erythrocytes and subsequently die with failure to produce definitive enucleated erythrocytes. The fetal liver of mutant mice contains erythroid and megakaryocytic precursors arrested in their development. Myelopoiesis is normal. Therefore, Gfi-1b is an essential transcriptional regulator of erythroid and megakaryocyte development.

• Transcription factor
• hematopoiesis
• development
• oncogene

Footnotes

• ↵3 Present address: Department of Pediatrics and of Molecular Biology and Oncology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA.

• ↵4 Corresponding author.

• E-MAIL stuart_orkin{at}dfci.harvard.edu; FAX (617) 738-5922.

• Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.959102.

• • Received November 1, 2001.
  • Accepted December 6, 2001.

• Cold Spring Harbor Laboratory Press

•