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.