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

doi:10.1182/blood-2005-04-1739

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

17 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 language	English
Journal	Blood
Volume	106
Issue number	10
Pages (from-to)	3396-404
Number of pages	8
ISSN	0006-4971
DOIs	https://doi.org/10.1182/blood-2005-04-1739
Publication status	Published - 2005

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@article{83a72320abfc11ddb5e9000ea68e967b,

title = "MEK kinase 1 activity is required for definitive erythropoiesis in the mouse fetal liver.",

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.",

author = "Barbara Bonnesen and Cathrine {\O}rskov and Susanne Rasmussen and Holst, {Peter Johannes} and Christensen, {Jan Pravsgaard} and Eriksen, {Karsten Wessel} and Klaus Qvortrup and Niels Odum and Tord Labuda",

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

year = "2005",

doi = "10.1182/blood-2005-04-1739",

language = "English",

volume = "106",

pages = "3396--404",

journal = "Blood",

issn = "0006-4971",

publisher = "American Society of Hematology",

number = "10",

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TY - JOUR

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

SN - 0006-4971

VL - 106

SP - 3396

EP - 3404

JO - Blood

JF - Blood

IS - 10

ER -

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

Abstract

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