The Journal of Experimental Medicine
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Published 1 April 2002. doi:10.1084/jem.20011522
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© Rockefeller University Press, 0022-1007/2002/4/941/ $5.00
The Journal of Experimental Medicine, Volume 195, Number 7, April 1, 2002 941-952

Original Article

Zinc Finger Protein, Hzf, Is Required for Megakaryocyte Development and Hemostasis

Yuki Kimura1, Adam Hart1, Masanori Hirashima1, Chen Wang2, Doug Holmyard2, Jackie Pittman2, Xin-Li Pang1, Carl W. Jackson3 and Alan Bernstein1,4,5

1 Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, M5G 1X5, Canada
2 Department of Pathology, Mount Sinai Hospital, Toronto, Ontario, M5G 1X5, Canada
3 The Division of Experimental Hematology, St. Jude Children's Research Hospital, Memphis, TN 38105
4 Department of Medical Genetics and Biophysics, University of Toronto, Toronto, Ontario, M5S 1A8, Canada
5 Canadian Institutes of Health Research, Ottawa, Ontario, K1A 0W9, Canada

Address correspondence to Alan Bernstein, Samuel Lunenfeld Research Institute of Mount Sinai Hospital, 600 University Ave., Rm. 982, Toronto, Ontario, Canada, M5G 1X5. Phone: 416-586-8273; Fax: 416-586-8857; E-mail: bernstein{at}mshri.on.ca

Using an expression gene trapping strategy, we recently identified a novel gene, hematopoietic zinc finger (Hzf), which encodes a protein containing three C2H2-type zinc fingers that is predominantly expressed in megakaryocytes. Here, we have examined the in vivo function of Hzf by gene targeting and demonstrated that Hzf is essential for megakaryopoiesis and hemostasis in vivo. Hzf-deficient mice exhibited a pronounced tendency to rebleed and had reduced {alpha}-granule substances in both megakaryocytes and platelets. These mice also had large, faintly stained platelets, whereas the numbers of both megakaryocytes and platelets were normal. These results indicate that Hzf plays important roles in regulating the synthesis of {alpha}-granule substances and/or their packing into {alpha}-granules during the process of megakaryopoiesis.

Key Words: {alpha}-granules • hemorrhage • hemostasis • megakaryopoiesis • thrombopoiesis


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