| First Author | Waskow C | Year | 2004 |
| Journal | Blood | Volume | 104 |
| Issue | 6 | Pages | 1688-95 |
| PubMed ID | 15178584 | Mgi Jnum | J:92961 |
| Mgi Id | MGI:3055258 | Doi | 10.1182/blood-2004-04-1247 |
| Citation | Waskow C, et al. (2004) Rescue of lethal c-KitW/W mice by erythropoietin. Blood 104(6):1688-95 |
| abstractText | Homozygous natural white-spotted (W) mutations in the gene encoding the receptor tyrosine kinase c-Kit are associated with hypoplastic bone marrow, severe macrocytic anemia, and lethality during early postnatal life. c-Kit(W/W) mice can be rescued by wild-type hematopoietic stem cells (HSCs), but it is not known whether the lethality of c-Kit(W/W) mice is the result of HSC failure or defects specific for erythropoiesis. Here we show that transgenic expression of erythropoietin (EPO) can overcome the lethality caused by the c-Kit(W/W) mutation. In W mutant mice rescued by EPO, termed WEPO, erythrocyte colony-forming units (CFU-Es) are rescued to normal frequencies. Hence, Epo receptor signals can partially bypass the strict requirement for c-Kit signaling in erythropoiesis in the absence of c-Kit in vivo. Using a series of W and rescue mouse strains, we define here the erythropoietic threshold permitting survival in vivo. The lethality of c-Kit(W/W) mice has precluded analysis of this crucial receptor-ligand pair in adult stem/progenitor cells. Our strategy to generate viable c-Kit(W/W) mice will be useful to analyze the role of this important receptor tyrosine kinase in adult life in vivo. |
