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 α-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 α-granule substances and/or their packing into α-granules during the process of megakaryopoiesis.
Zinc Finger Protein, Hzf, Is Required for Megakaryocyte Development and Hemostasis
A. Hart's present address is The Walter and Eliza Hall Institute, PO Royal Melbourne Hospital, VIC 3050, Australia.
X.-L. Pang's present address is Arius Research, Inc., Mississauga, Ontario, L4V 1N3, Canada.
Abbreviations used in this paper: AChE, acetylcholinesterase; ES, embryonic stem; GP, glycoprotein; GPS, gray platelet syndrome; Hzf, hematopoietic zinc finger; IRES, internal ribosome-entry site; MGDF, megakaryocyte growth and development factor; neo, neomycin resistant gene; PDGF, platelet-derived growth factor; TPO, thrombopoietin; vWF, von Willebrand factor.
Yuki Kimura, Adam Hart, Masanori Hirashima, Chen Wang, Doug Holmyard, Jackie Pittman, Xin-Li Pang, Carl W. Jackson, Alan Bernstein; Zinc Finger Protein, Hzf, Is Required for Megakaryocyte Development and Hemostasis . J Exp Med 1 April 2002; 195 (7): 941–952. doi: https://doi.org/10.1084/jem.20011522
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