RAPID COMMUNICATION Deficiencies in Progenitor Cells of Multiple Hematopoietic Lineages and Defective Megakaryocytopoiesis in Mice Lacking the Thrombopoietin Receptor c-Mpl

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 mpT" mice, as was the distribution of morphologically identifiable precursors in hematopoietic tissues. Bone marrow and spleen cells of adult mpT" 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 mpT" mice, including multipotential, blast cell, and committed progeni-