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. Here we describe aberrant hematopoeisis and hemorrhaging in mouse embryos homozygous for a targeted disruption in the Ets family member, Fli1. Mutant embryos are found to hemorrhage from the dorsal aorta to the lumen of the neural tube and ventricles of the brain (hematorrhachis) on embryonic day 11.0 (E11.0) and are dead by E12.5. Histological examinations and in situ hybridization reveal disorganization of columnar epithelium and the presence of hematomas within the neuroepithelium and disruption of the basement membrane lying between this and mesenchymal tissues, both of which express Fli1 at the time of hemorrhaging. Livers from mutant embryos contain few pronormoblasts and basophilic normoblasts and have 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 cell line used for the generation of knockout lines. Taken together, these results provide in vivo evidence for the role of Fli1 in the regulation of hematopoiesis and hemostasis.
Spyropoulos
D D
DD
Center for Molecular and Structural Biology, Medical University of South Carolina, USA.
Pharr
P N
PN
Lavenburg
K R
KR
Jackers
P
P
Papas
T S
TS
Ogawa
M
M
Watson
D K
DK
D000818:Animals; D001921:Brain / Q000196:embryology / Q000503:physiopathology; D002478:Cells, Cultured; D002490:Central Nervous System / Q000196:embryology / Q000503:physiopathology; D004268:DNA-Binding Proteins / Q000235:genetics*; D005314:Embryonic and Fetal Development / Q000235:genetics; D005313:Fetal Death / Q000235:genetics*; D005822:Genetic Vectors; D006410:Hematopoiesis / Q000235:genetics*; D006470:Hemorrhage / Q000235:genetics*; D006579:Heterozygote; D008099:Liver / Q000196:embryology; D051379:Mice; D018345:Mice, Knockout; D051789:Proto-Oncogene Protein c-fli-1; D011518:Proto-Oncogene Proteins; D011995:Recombination, Genetic; D015534:Trans-Activators / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
D004268:DNA-Binding Proteins; C497426:Fli1 protein, mouse; D051789:Proto-Oncogene Protein c-fli-1; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D014157:Transcription Factors