Synergistic effects on erythropoiesis, thrombopoiesis, and stem cell competitiveness in mice deficient in thrombopoietin and steel factor receptors

Abstract

The degree of redundancy between thrombopoietin (Tpo) and steel factor (SF) cytokine pathways in the regulation of hematopoiesis was investigated by generating mice lacking both c-Mpl and fully functional c-Kit receptors. Double-mutant c-Mpl(-/-)Kit(Wv/Wv) mice exhibited reduced viability, making up only 2% of the offspring from c-Mpl(-/-)Kit(Wv/)(+) intercrosses. The thrombocytopenia and megakaryocytopenia characteristic of c-Mpl(-/-) mice was unchanged in c-Mpl(-/-)Kit(Wv/Wv) mice. However, the number of megakaryocytic colony forming units (CFU-Mks) was significantly reduced, particularly in the spleen. While Kit(Wv/Wv) mice, but not c-Mpl(-/-) mice, are anemic, the anemia was more severe ..