The zinc-finger proto-oncogene Gfi-1b is essential for development of the erythroid and megakaryocytic lineages.
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.
Saleque
Shireen
S
Department of Pediatric Oncology, Children's Hospital, Dana Farber Cancer Institute, Harvard Medical School, and Howard Hughes Medical Institute, Boston, Massachusetts 02115, USA.
Cameron
Scott
S
Orkin
Stuart H
SH
D000818:Animals; D019070:Cell Lineage; D004622:Embryo, Mammalian / Q000502:physiology*; D004912:Erythrocytes / Q000166:cytology*; D004920:Erythropoiesis / Q000502:physiology*; D005434:Flow Cytometry; D015870:Gene Expression; D006410:Hematopoiesis / Q000502:physiology*; D008533:Megakaryocytes / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D012097:Repressor Proteins / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016335:Zinc Fingers / Q000502:physiology*
C486395:Gfi1b protein, mouse; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins