Deregulated expression of c-myc in megakaryocytes of transgenic mice increases megakaryopoiesis and decreases polyploidization

Alexander Thompson, Ying Zhang, Dimitry Kamen, Carl W. Jackson, Robert Cardiff, Katya Ravid

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)22976-22982
Number of pages7
JournalJournal of Biological Chemistry
Volume271
Issue number38
DOIs
StatePublished - Sep 30 1996

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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