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Constitutive expression of Mpl ligand transcripts during thrombocytopenia
or thrombocytosis
K Cohen-Solal, JL Villeval, M Titeux, S Lok, W Vainchenker and F Wendling
INSERM U 362, Institut Gustave Roussy, Villejuif, France.
Mpl ligand (thrombopoietin [TPO]) is the physiological regulator of
platelet production. In mice, mRNA encoding the Mpl ligand (Mpl-L) is
predominantly found by Northern blot analysis in the liver and kidney. To
investigate the mode of regulation of the Mpl-L gene, we have developed
several experimental models of severe thrombocytopenia differing in their
kinetics and an opposite model of chronic thrombocytosis. Northern analysis
performed at various times after induction of a thrombocytopenic state
demonstrates that, whatever the number of circulating platelets, no change
in Mpl-L mRNA level occurs in liver and kidney. By ribonuclease protection
assays, we analyzed the ratios between mRNAs coding for the wild-type Mpl-L
form and various splice variants encoding inactive or nonsecreted Mpl-L
proteins. No modification in levels of these various isoforms was detected
confirming the data of a previous report. Because the highest level of
Mpl-L bioactivity in sera was observed only in mice with drastically
reduced numbers of both platelets and megakaryocytes, these results further
suggest that not only platelets, but also megakaryocytes, must be involved
in the regulation of the level of circulating Mpl-L. In addition, we show
that no downregulation of wild-type Mpl-L mRNA and no change in the ratio
of Mpl-L mRNA isoforms were detected in mice in which a chronic
thrombocytosis was induced. Together, these different models extend and
further confirm that the regulation of Mpl-L does not occur at a
transcriptional level or by a modulation in the ratios of Mpl-L mRNA
isoforms.
Volume 88,
Issue 7,
pp. 2578-2584,
10/01/1996
Copyright © 1996 by The American Society of Hematology

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