|
|
 Previous Article | Table of Contents | Next Article 
A 2.7-kb Portion of the 5' Flanking Region of the Murine Glycoprotein  IIb Gene Is Transcriptionally Active in Primitive Hematopoietic Progenitor Cells
Philippe Tropel,
Valérie Roullot,
Muriel Vernet,
Christel Poujol,
Hervé Pointu,
Paquita Nurden,
Gérard Marguerie, and
Diana Tronik-Le Roux
From the Commissariat à l'Energie Atomique (CEA), Laboratoire de Transgenèse et Différenciation Cellulaire, Département de Biologie Moléculaire et Structurale, CEA-Grenoble, Grenoble Cedex; and Laboratoire d'Hemobiologie, U.M.R. 5533 CNRS - Hôpital Cardiologique, Pessac, France.
The continuous generation of mature blood cells from primitive multipotent progenitor cells requires a highly complex series of cellular events that are still largely unknown. To examine the molecular events associated with the commitment of these hematopoietic progenitor cells to the megakaryocytic lineage, the  subunit of the platelet integrin IIb 3 was used as marker. Despite an abundance of information regarding the role of this integrin in platelet adhesion and aggregation, the mechanisms that control the expression of the genes that code for these proteins are poorly understood and the earliest hematopoietic cell capable of expressing them has not been clearly identified. Thus, a strategy was developed to eradicate, using a conditional toxigene, all the hematopoietic cells capable of expressing the IIb gene in mice. This was achieved by targeting the expression of the gene encoding the herpes simplex virus thymidine kinase (tk), specifically to these cell types, using a 2.7-kb fragment of the 5'-flanking region of the murine IIb gene. Three transgenic lines having 1, 3, and 4 copies of the transgene, respectively were produced and analyzed. Administration of ganciclovir (GCV) to these mice induced a severe thrombocytopenia, which was due to the depletion of the entire megakaryocytic lineage, as shown by bone marrow (BM) culture and electron microscopy analysis. The time required to attain a severe thrombocytopenia was dependent on the level of the expression of the transgene and varied from 7 to 11 days. This condition was completely reversed when GCV treatment was discontinued. Progenitor cell assays showed that the IIb promoter was active in primitive hematopoietic progenitor cells possessing myeloid, erythroid, and megakaryocytic potential and that the transcriptional activity of the promoter decreased progressively as differentiation proceeded towards the erythroid and myeloid lineages.
Blood, Vol. 90 No. 8 (July 15), 1997:
pp. 2995-3004
© 1997 by The American Society of Hematology.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
R. Tiedt, T. Schomber, H. Hao-Shen, and R. C. Skoda
Pf4-Cre transgenic mice allow the generation of lineage-restricted gene knockouts for studying megakaryocyte and platelet function in vivo
Blood,
February 15, 2007;
109(4):
1503 - 1506.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Ohmori, J. Mimuro, K. Takano, S. Madoiwa, Y. Kashiwakura, A. Ishiwata, M. Niimura, K. Mitomo, T. Tabata, M. Hasegawa, et al.
Efficient expression of a transgene in platelets using simian immunodeficiency virus-based vector harboring glycoprotein Ib{alpha} promoter: in vivo model for platelet-targeting gene therapy
FASEB J,
July 1, 2006;
20(9):
1522 - 1524.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Oki, J. Kitaura, K. Eto, Y. Lu, M. Maeda-Yamamoto, N. Inagaki, H. Nagai, Y. Yamanishi, H. Nakajina, H. Kumagai, et al.
Integrin {alpha}IIb{beta}3 Induces the Adhesion and Activation of Mast Cells through Interaction with Fibrinogen
J. Immunol.,
January 1, 2006;
176(1):
52 - 60.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Jacquelin, T. Kortulewski, P. Vaigot, A. Pawlik, G. Gruel, O. Alibert, P. Soularue, C. Joubert, X. Gidrol, and D. T.-L. Roux
Novel pathway for megakaryocyte production after in vivo conditional eradication of integrin {alpha}IIb-expressing cells
Blood,
September 15, 2005;
106(6):
1965 - 1974.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. J. Ferkowicz, M. Starr, X. Xie, W. Li, S. A. Johnson, W. C. Shelley, P. R. Morrison, and M. C. Yoder
CD41 expression defines the onset of primitive and definitive hematopoiesis in the murine embryo
Development,
September 15, 2003;
130(18):
4393 - 4403.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. T. Mitjavila-Garcia, M. Cailleret, I. Godin, M. M. Nogueira, K. Cohen-Solal, V. Schiavon, Y. Lecluse, F. Le Pesteur, A. H. Lagrue, and W. Vainchenker
Expression of CD41 on hematopoietic progenitors derived from embryonic hematopoietic cells
Development,
March 6, 2003;
129(8):
2003 - 2013.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. A. Thornton, C. Zhang, M. A. Kowalska, and M. Poncz
Identification of distal regulatory regions in the human alpha IIb gene locus necessary for consistent, high-level megakaryocyte expression
Blood,
November 15, 2002;
100(10):
3588 - 3596.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Zhang, M. A. Thornton, M. A. Kowalska, B. S. Sachis, M. Feldman, M. Poncz, S. E. McKenzie, and M. P. Reilly
Localization of distal regulatory domains in the megakaryocyte-specific platelet basic protein/platelet factor 4 gene locus
Blood,
August 1, 2001;
98(3):
610 - 617.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Debili, C. Robin, V. Schiavon, R. Letestu, F. Pflumio, M.-T. Mitjavila-Garcia, L. Coulombel, and W. Vainchenker
Different expression of CD41 on human lymphoid and myeloid progenitors from adults and neonates
Blood,
April 1, 2001;
97(7):
2023 - 2030.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Gaur, G. J. Murphy, F. J. deSauvage, and A. D. Leavitt
Characterization of Mpl mutants using primary megakaryocyte-lineage cells from mpl{-}/{-} mice: a new system for Mpl structure-function studies
Blood,
March 15, 2001;
97(6):
1653 - 1661.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Lepage, M. Leboeuf, J.-P. Cazenave, C. de la Salle, F. Lanza, and G. Uzan
The alpha IIbbeta 3 integrin and GPIb-V-IX complex identify distinct stages in the maturation of CD34+ cord blood cells to megakaryocytes
Blood,
December 15, 2000;
96(13):
4169 - 4177.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Jandrot-Perrus, S. Busfield, A.-H. Lagrue, X. Xiong, N. Debili, T. Chickering, J.-P. L. Couedic, A. Goodearl, B. Dussault, C. Fraser, et al.
Cloning, characterization, and functional studies of human and mouse glycoprotein VI: a platelet-specific collagen receptor from the immunoglobulin superfamily
Blood,
September 1, 2000;
96(5):
1798 - 1807.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. T.-L. Roux, V. Roullot, C. Poujol, T. Kortulewski, P. Nurden, and G. Marguerie
Thrombasthenic mice generated by replacement of the integrin alpha IIb gene: demonstration that transcriptional activation of this megakaryocytic locus precedes lineage commitment
Blood,
August 15, 2000;
96(4):
1399 - 1408.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. A. Wilcox, J. C. Olsen, L. Ishizawa, P. F. Bray, D. L. French, D. A. Steeber, W. R. Bell, M. Griffith, and G. C. White II
Megakaryocyte-targeted synthesis of the integrin beta 3-subunit results in the phenotypic correction of Glanzmann thrombasthenia
Blood,
June 15, 2000;
95(12):
3645 - 3651.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. M. Vannucchi, F. Paoletti, S. Linari, C. Cellai, R. Caporale, P. R. Ferrini, M. Sanchez, G. Migliaccio, and A. R. Migliaccio
Identification and characterization of a bipotent (erythroid and megakaryocytic) cell precursor from the spleen of phenylhydrazine-treated mice
Blood,
April 15, 2000;
95(8):
2559 - 2568.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Letestu, N. Vitrat, A. Masse, J.-P. L. Couedic, V. Lazar, P. Rameau, F. Wendling, J. Vuillier, P. Boutard, E. Plouvier, et al.
Existence of a differentiation blockage at the stage of a megakaryocyte precursor in the thrombocytopenia and absent radii (TAR) syndrome
Blood,
March 1, 2000;
95(5):
1633 - 1641.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Gomez-Espuch, J. Corral, R. Gonzalez-Conejero, F. Ortuno, J.M. Moraleda, V. Vicente;, C. Ody, B. A. Imhof, and C. Corbel
Glycoprotein IIb/IIIa Expression on Hematopoietic Stem Cells: Constitutive Expression or Platelet Adhesion?
Blood,
November 1, 1999;
94(9):
3271 - 3273.
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. A. Wilcox, J. C. Olsen, L. Ishizawa, M. Griffith, and G. C. White II
Integrin alpha IIb promoter-targeted expression of gene products in megakaryocytes derived from retrovirus-transduced human hematopoietic cells
PNAS,
August 17, 1999;
96(17):
9654 - 9659.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Ody, P. Vaigot, P. Quere, B. A. Imhof, and C. Corbel
Glycoprotein IIb-IIIa Is Expressed on Avian Multilineage Hematopoietic Progenitor Cells
Blood,
May 1, 1999;
93(9):
2898 - 2906.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Poujol, D. T.-L. Roux, P. Tropel, V. Roullot, A. Nurden, G. Marguerie, and P. Nurden
Ultrastructural Analysis of Bone Marrow Hematopoiesis in Mice Transgenic for the Thymidine Kinase Gene Driven by the alpha IIb Promoter
Blood,
September 15, 1998;
92(6):
2012 - 2023.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
