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| TRANSCRIPTION FACTOR NF-E2 IS REQUIRED FOR PLATELET FORMATION INDEPENDENT OF THE ACTIONS OF THROMBOPOIETIN/MGDF IN MEGAKARYOCYTE DEVELOPMENT |
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| Author(s): SHIVDASANI RA, ROSENBLATT MF, ZUCKERFRANKLIN D, JACKSON CW, HUNT P, SARIS CJM, ORKIN SH |
| Source: CELL Volume: 81 Issue: 5 Pages: 695-704 Published: JUN 2 1995 |
| Times Cited: 426 References: 65 |
| Abstract: Despite the importance of blood platelets in health and disease, the mechanisms regulating their formation within megakaryocytes are unknown. We generated mice lacking the hematopoietic subunit (p45) of the heterodimeric erythroid transcription factor NF-E2. Unexpectedly, NF-E2(-/-) mice lack circulating platelets and die of hemorrhage; their megakaryocytes show no cytoplasmic platelet formation. Though platelets are absent, serum levels of the growth factor thrombopoietin/MGDF are not elevated above controls. Nonetheless, NF-E2(-/-) megakaryocytes proliferate in vivo in response to thrombopoietin administration. Thus, as an essential factor for megakaryocyte maturation and platelet production, NF-ES must regulate critical target genes independent of the action of thrombopoietin. These findings provide insight into the genetic analysis of megakaryocyte maturation and thrombopoiesis. |
| Document Type: Article |
| Language: English |
| Reprint Address: SHIVDASANI, RA (reprint author), DANA FARBER CANC INST, DIV MED ONCOL, BOSTON, MA 02115 USA |
Addresses:
1. HARVARD UNIV, SCH MED, DEPT MED, BOSTON, MA USA
2. CHILDRENS HOSP, HOWARD HUGHES MED INST, BOSTON, MA USA
3. CHILDRENS HOSP, DIV HEMATOL ONCOL, BOSTON, MA USA
4. HARVARD UNIV, SCH MED, DEPT PEDIAT, BOSTON, MA 02115 USA
5. NYU, MED CTR, DEPT MED, NEW YORK, NY 10016 USA
6. ST JUDE CHILDRENS HOSP, DIV EXPTL HEMATOL, MEMPHIS, TN 38105 USA
7. AMGEN INC, AMGEN CTR, THOUSAND OAKS, CA 91320 USA |
| Publisher: CELL PRESS, 50 CHURCH ST CIRCULATION DEPT, CAMBRIDGE, MA 02138 |
| Subject Category: Biochemistry & Molecular Biology; Cell Biology |
| IDS Number: RB961 |
| ISSN: 0092-8674 |
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