[en] 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.
Research center :
Hollings Cancer Center, Medical University of South Carolina, USA
Spyropoulos, Demetri D.; Medical University of South Carolina > Hollings Cancer Center > Center for Molecular and Structural Biology
Pharr, Pamela N.; Medical University of South Carolina > Department of Medicine and Ralph H. Johnson VA Medical Center
Lavenburg, Kim R.; Medical University of South Carolina > Center for Molecular and Strucural Biology
Jackers, Pascale ; Medical University of South Carolina > Center for Molecular and Structural Biology
Papas, Takis S.; Medical University of South Carolina > Hollings Cancer Center and Department of Medicine > Center for Molecular and Structural Biology
Ogawa, Makio; Medical University of South carolina > Hollings Cancer Center and Department of Medicine and Ralph H. Johnson VA Medical Center
Watson, Dennis K.; Medical University of South Carolina > Hollings Cancer Center > Center for Molecular and Structural Biology
Language :
English
Title :
Hemorrhage, impaired hematopoiesis, and lethality in mouse embryos carrying a targeted disruption of the Fli1 transcription factor.
Publication date :
August 2000
Journal title :
Molecular and Cellular Biology
ISSN :
0270-7306
eISSN :
1098-5549
Publisher :
American Society for Microbiology (ASM), Washington, United States - District of Columbia
Volume :
20
Issue :
15
Pages :
5643-5652
Peer reviewed :
Peer Reviewed verified by ORBi
Name of the research project :
"Role of the Ets-1 and Fli-1 transcription factors in cellular differentiation and development"
Funders :
Grant of the "NCI National Institute of Health" (PO1 CA78582) Exchange Visitor Program P-1-715
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