MEK kinase 1 activity is required for definitive erythropoiesis in the mouse fetal liver.
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MEK kinase 1 activity is required for definitive erythropoiesis in the mouse fetal liver. / Bonnesen, Barbara; Ørskov, Cathrine; Rasmussen, Susanne; Holst, Peter Johannes; Christensen, Jan Pravsgaard; Eriksen, Karsten Wessel; Qvortrup, Klaus; Odum, Niels; Labuda, Tord.
I: Blood, Bind 106, Nr. 10, 2005, s. 3396-404.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - MEK kinase 1 activity is required for definitive erythropoiesis in the mouse fetal liver.
AU - Bonnesen, Barbara
AU - Ørskov, Cathrine
AU - Rasmussen, Susanne
AU - Holst, Peter Johannes
AU - Christensen, Jan Pravsgaard
AU - Eriksen, Karsten Wessel
AU - Qvortrup, Klaus
AU - Odum, Niels
AU - Labuda, Tord
N1 - Keywords: Animals; Cell Nucleus; DNA; Embryo, Mammalian; Erythropoiesis; Hematopoiesis, Extramedullary; Hemoglobins; Liver; Liver Transplantation; MAP Kinase Kinase Kinase 1; Macrophages; Mice; Mice, Knockout
PY - 2005
Y1 - 2005
N2 - 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.
AB - 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.
U2 - 10.1182/blood-2005-04-1739
DO - 10.1182/blood-2005-04-1739
M3 - Journal article
C2 - 16081685
VL - 106
SP - 3396
EP - 3404
JO - Blood
JF - Blood
SN - 0006-4971
IS - 10
ER -
ID: 8441600