| First Author | Bonnesen B | Year | 2005 |
| Journal | Blood | Volume | 106 |
| Issue | 10 | Pages | 3396-404 |
| PubMed ID | 16081685 | Mgi Jnum | J:124072 |
| Mgi Id | MGI:3720458 | Doi | 10.1182/blood-2005-04-1739 |
| Citation | Bonnesen B, et al. (2005) MEK kinase 1 activity is required for definitive erythropoiesis in the mouse fetal liver. Blood 106(10):3396-404 |
| abstractText | Mitogen-activated protein kinase/extracellular signal to regulated kinase (MEK) kinase 1 (MEKK1) is a c-Jun N-terminal kinase (JNK) activating kinase known to be implicated in proinflammatory responses and cell motility. Using mice deficient for MEKK1 kinase activity (Mekk1(DeltaKD)) we show a role for MEKK1 in definitive mouse erythropoiesis. Although Mekk1(DeltaKD) mice are alive and fertile on a 129 x C57/BL6 background, the frequency of Mekk1(DeltaKD) embryos that develop past embryonic day (E) 14.5 is dramatically reduced when backcrossed into the C57/BL6 background. At E13.5, Mekk1(DeltaKD) embryos have normal morphology but are anemic due to failure of definitive erythropoiesis. When Mekk1(DeltaKD) fetal liver cells were transferred to lethally irradiated wild-type hosts, mature red blood cells were generated from the mutant cells, suggesting that MEKK1 functions in a non-cell-autonomous manner. Based on immunohistochemical and hemoglobin chain transcription analysis, we propose that the failure of definitive erythropoiesis is due to a deficiency in enucleation activity caused by insufficient macrophage-mediated nuclear DNA destruction. |
