Hemorrhage, impaired hematopoiesis, and lethality in mouse embryos carrying a targeted disruption of the Fli1 transcription factor

The Ets family of transcription factors have been suggested to function as key regulators of hematopoeisis. sere we describe aberrant hematopoeisis an d hemorrhaging in mouse embryos homozygous for a targeted disruption in the Ets family member, Fli1. Mutant embryos are found to hemorrhage from the d orsal aorta to the lumen of the neural tube and ventricles of the brain (he matorrhachis) on embryonic day 11.0 (E11.0) and are dead by E12.5. Histolog ical examinations and in situ hybridization reveal disorganization of colum nar epithelium and the presence of hematomas within the neuroepithelium and disruption of the basement membrane lying between this and mesenchymal tis sues, both of which express Fli1 at the time of hemorrhaging. Livers from m utant embryos contain few pronormoblasts and basophilic normoblasts and hav e drastically reduced numbers of colony forming cells. These defects occur with complete penetrance of phenotype regardless of the genetic background (inbred B6, hybrid 129/B6, or outbred CD1) or the targeted embryonic stem c ell line used for the generation of knockout lines. Taken together, these r esults provide in vivo evidence for the role of Fli1 in the regulation of h ematopoiesis and hemostasis.