| First Author | Antonchuk J | Year | 2004 |
| Journal | Blood | Volume | 104 |
| Issue | 5 | Pages | 1306-13 |
| PubMed ID | 15138166 | Mgi Jnum | J:92703 |
| Mgi Id | MGI:3054317 | Doi | 10.1182/blood-2004-04-1522 |
| Citation | Antonchuk J, et al. (2004) Synergistic effects on erythropoiesis, thrombopoiesis, and stem cell competitiveness in mice deficient in thrombopoietin and steel factor receptors. Blood 104(5):1306-13 |
| abstractText | 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 in double-mutant c-Mpl(-/-)Kit(Wv/Wv) mice, indicating redundancy between Tpo and SF in erythropoiesis. At the primitive cell level, c-Mpl(-/-) and Kit(Wv/Wv) mice have similar phenotypes, including reduced progenitors, colony forming units-spleen (CFU-Ss), and repopulating activities. All of these parameters were exacerbated in double-mutant mice. c-Mpl(-/-)Kit(Wv/Wv) mice had 8-fold fewer clonogenic progenitor cells and at least 28-fold fewer CFU-Ss. c-Mpl(-/-) mice also demonstrated a reduced threshold requirement for nonmyeloablative transplant repopulation, a trait previously associated only with Kit(W) mice, and the level of nonmyeloablative engraftment was significantly greater in c-Mpl(-/-) Kit(Wv/Wv) double mutants. Thus, c-Mpl(-/-) Kit(Wv/Wv) mice reveal nonredundant and synergistic effects of Tpo and SF on primitive hematopoietic cells. |
