Deficiencies in progenitor cells of multiple hematopoietic lineages and defective megakaryocytopoiesis in mice lacking the thrombopoietin receptor c-mpl
- Author(s)
- Alexander, WS; Roberts, AW; Nicola, NA; Li, RL; Metcalf, D;
- Details
- Publication Year 1996-03-15,Volume 87,Issue #6,Page 2162-2170
- Journal Title
- BLOOD
- Publication Type
- Journal Article
- Abstract
- Mice with a null mutation in the thrombopoietin (TPO) receptor c-Mpl were generated by gene targeting. c-mpl-deficient mice developed normally but were deficient in megakaryocytes and severely thrombocytopenic, The hematocrit and numbers of mature circulating leukocytes were normal in mpl(-/-) mice, as was the distribution of morphologically identifiable precursors in hematopoietic tissues, Bone marrow and spleen cells of adult mpl(-/-) mice lacked specific binding sites for TPO, were unresponsive to TPO in culture, and displayed a marked deficiency in progenitor cells with megakaryocytic potential, Significantly, total hematopoietic progenitor cell numbers were also reduced in mpl(-/-) mice, including multipotential, blast cell, and committed progenitors of multiple lineages. The megakaryocyte deficiency was evident as early as 14 days of gestation in mpl-deficient mice, although reductions in progenitor cell numbers arose only later in development. The data suggest that the critical function of c-Mpl signalling in megakaryocytopoiesis is in maintenance of mature megakaryocyte numbers through control of progenitor cell proliferation and maturation, Moreover, our results also imply an important role for TPO and c-Mpl in the production of primitive pluripotent progenitor cells as well as progenitor cells committed to nonmegakaryocytic lineages. (C) 1996 by The American Society of Hematology.
- Publisher
- W B SAUNDERS CO
- Keywords
- MONOCLONAL-ANTIBODY; DIFFERENTIATION ANTIGENS; MOUSE MACROPHAGE; EXPRESSION; IDENTIFICATION; SUPERFAMILY; CLONING
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- Refer to copyright notice on published article.
Creation Date: 1996-03-15 12:00:00