Low levels of erythroid and myeloid progenitors in thrombopoietin- and c- mpl-deficient mice

Karen Carver-Moore, Hal E. Broxmeyer, Shiuh Ming Luoh, Scott Cooper, Jipeng Peng, Samuel A. Burstein, Mark W. Moore, Frederic J. De Sauvage

Research output: Contribution to journalArticle

244 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)803-808
Number of pages6
JournalBlood
Volume88
Issue number3
StatePublished - Aug 1 1996
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Carver-Moore, K., Broxmeyer, H. E., Luoh, S. M., Cooper, S., Peng, J., Burstein, S. A., Moore, M. W., & De Sauvage, F. J. (1996). Low levels of erythroid and myeloid progenitors in thrombopoietin- and c- mpl-deficient mice. Blood, 88(3), 803-808.