MEK kinase 1 activity is required for definitive erythropoiesis in the mouse fetal liver.

Barbara Bonnesen, Cathrine Ørskov, Susanne Rasmussen, Peter Johannes Holst, Jan Pravsgaard Christensen, Karsten Wessel Eriksen, Klaus Qvortrup, Niels Odum, Tord Labuda

Research output: Contribution to journalJournal articleResearchpeer-review

18 Citations (Scopus)

Abstract

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.
Original languageEnglish
JournalBlood
Volume106
Issue number10
Pages (from-to)3396-404
Number of pages8
ISSN0006-4971
DOIs
Publication statusPublished - 2005

Bibliographical note

Keywords: Animals; Cell Nucleus; DNA; Embryo, Mammalian; Erythropoiesis; Hematopoiesis, Extramedullary; Hemoglobins; Liver; Liver Transplantation; MAP Kinase Kinase Kinase 1; Macrophages; Mice; Mice, Knockout

Cite this