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 language | English (US) |
|---|---|
| Pages (from-to) | 22976-22982 |
| Number of pages | 7 |
| Journal | Journal of Biological Chemistry |
| Volume | 271 |
| Issue number | 38 |
| DOIs | |
| State | Published - Sep 30 1996 |
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ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Cell Biology
Cite this
Deregulated expression of c-myc in megakaryocytes of transgenic mice increases megakaryopoiesis and decreases polyploidization. / Thompson, Alexander; Zhang, Ying; Kamen, Dimitry; Jackson, Carl W.; Cardiff, Robert; Ravid, Katya.
In: Journal of Biological Chemistry, Vol. 271, No. 38, 30.09.1996, p. 22976-22982.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Deregulated expression of c-myc in megakaryocytes of transgenic mice increases megakaryopoiesis and decreases polyploidization
AU - Thompson, Alexander
AU - Zhang, Ying
AU - Kamen, Dimitry
AU - Jackson, Carl W.
AU - Cardiff, Robert
AU - Ravid, Katya
PY - 1996/9/30
Y1 - 1996/9/30
N2 - 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.
AB - 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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U2 - 10.1074/jbc.271.38.22976
DO - 10.1074/jbc.271.38.22976
M3 - Article
VL - 271
SP - 22976
EP - 22982
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 38
ER -