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Volume 271, Number 38,
Issue of September 20, 1996
pp. 22976-22982
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.
Deregulated Expression of c-myc in Megakaryocytes of
Transgenic Mice Increases Megakaryopoiesis and Decreases
Polyploidization
(Received for publication, January 25, 1996, and in revised form, May 31, 1996)
Alexander
Thompson
,
Ying
Zhang
,
Dimitry
Kamen
,
Carl W.
Jackson
§
,
Robert D.
Cardiff
¶
and
Katya
Ravid
From the Department of Biochemistry, Boston
University School of Medicine, Boston, Massachusetts 02139, the
§ Division of Experimental Hematology, St. Jude Children's
Research Hospital, Memphis, Tennessee 38105, and the ¶ Department
of Medical Pathology, University of California at Davis, Sacramento,
California 95817
Platelets, essential for vascular integrity and
hemostasis, fragment from polyploid megakaryocytes, characterized by
their endomitotic cell cycle. We studied the influence of
overexpression of c-myc oncogene on megakaryopoiesis and
endomitosis in vivo, using transgenic mice carrying
c-myc fused to the estrogen receptor under the control of
the platelet factor 4 (PF4) megakaryocyte-specific promoter. The
rationale behind this strategy was to obtain controlled overexpression
of an active c-Myc, depending on the estrogen level in the mouse
circulation. Analysis of these transgenic mice revealed that the bone
marrow of female transgenic mice or of estrogen-injected male
transgenic mice, but not of age-matched transgenic males nor
nontransgenic females, contained frequent immature myeloid cells and an
increased number of megakaryocytes. Deregulated expression of c-Myc
shifted the normal ploidy profile of megakaryocytes due to a
significant increase in proliferating megakaryocytes and a decrease in
the fraction of ploidizing cells. These transgenic mice represent a
novel in vivo model for a Myc-induced myeloproliferative
disorder which can be controlled.

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Copyright © 1996 by the American Society for Biochemistry and Molecular Biology.
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