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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.

dagger 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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