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Molecular and Cellular Biology, August 2000, p. 5643-5652, Vol. 20, No. 15
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Hemorrhage, Impaired Hematopoiesis, and Lethality in Mouse
Embryos Carrying a Targeted Disruption of the Fli1
Transcription Factor
Demetri D.
Spyropoulos,1,2
Pamela N.
Pharr,3,4
Kim R.
Lavenburg,1
Pascale
Jackers,1
Takis S.
Papas,1,2,3
Makio
Ogawa,2,3,4 and
Dennis K.
Watson1,2,*
Center for Molecular and Structural
Biology,1 Hollings Cancer
Center,2 and Department of
Medicine,3 Medical University of South
Carolina, and Ralph H. Johnson VA Medical
Center,4 Charleston, South Carolina 29425
Received 21 January 2000/Returned for modification 20 March
2000/Accepted 25 April 2000
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.
*
Corresponding author. Mailing address: Center for
Molecular and Structural Biology, Hollings Cancer Center, Medical
University of South Carolina, Charleston, SC 29425. Phone: (843)
792-3900. Fax: (843) 792-3940. E-mail: watsondk{at}musc.edu.

This paper is dedicated to the memory of Takis S. Papas, a mentor,
scientific colleague, and
friend.
Molecular and Cellular Biology, August 2000, p. 5643-5652, Vol. 20, No. 15
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
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