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Low levels of erythroid and myeloid progenitors in thrombopoietin-and c-
mpl-deficient mice
K Carver-Moore, HE Broxmeyer, SM Luoh, S Cooper, J Peng, SA Burstein, MW Moore and FJ de Sauvage
Department of Molecular Oncology, Genentech, Inc, South San Francisco, CA
94080, USA.
Thrombopoietin (TPO), the ligand for the c-mpl receptor, has been shown to
be the major regulator of platelet production. Mice deficient in either
c-mpl or TPO generated by homologous recombination show a dramatic decrease
in platelet counts, but other blood cell counts are normal. Because TPO
treatment of myelosuppressed mice not only enhances the recovery of
platelets but also accelerates erythroid recovery, we investigated the
levels of myeloid and erythroid progenitor cells in TPO-or c-mpl-deficient
mice. Our results show that the number of megakaryocyte,
granulocyte-macrophage, erythroid, and multilineage progenitors are
significantly reduced in the bone marrow, spleen, and peripheral blood of
either TPO-or c-mpl-deficient mice. Administration of recombinant murine
TPO to TPO-deficient mice and control littermate mice significantly
increased the absolute number of myeloid, erythroid, and mixed progenitors
in bone marrow and spleen. This increase was especially apparent in
TPO-deficient mice where numbers were increased to a level greater than in
diluent-treated control mice and approached or equaled that in the
TPO-treated control mice. Moreover, TPO- administration greatly increased
the number of circulating progenitors as well as platelets in both
TPO-deficient and control mice. Furthermore, the megakaryocytopoietic
activity of other cytokines in the absence of a functional TPO or c-mpl
gene was shown both in vitro and in vivo.
Volume 88,
Issue 3,
pp. 803-808,
08/01/1996
Copyright © 1996 by The American Society of Hematology
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89(6):
1896 - 1904.
[Abstract]
[Full Text]
[PDF]
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