Abstract
Janus kinases (Jaks) play an important role in signal transduction via cytokine and growth factor receptors. A targeted inactivation of Jak2 was performed. Jak2-/- embryos are anemic and die around day 12.5 postcoitum. Primitive erythrocytes are found, but definitive erythropoiesis is absent. Compared to erythropoietin receptor-deficient mice, the phenotype of Jak2 deficiency is more severe. Fetal liver BFU-E and CFU-E colonies are completely absent. However, multilineage hematopoietic stem cells (CD34low, c-kit(pos)) can be found, and B lymphopoiesis appears intact. In contrast to IFNalpha stimulation, Jak2-/- cells do not respond to IFNgamma. Jak2-/- embryonic stem cells are competent for LIF signaling. The data provided demonstrate that Jak2 has pivotal functions for signal transduction of a set of cytokine receptors required in definitive erythropoiesis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Anemia
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Animals
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B-Lymphocytes / cytology
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Cytokines / pharmacology
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DNA-Binding Proteins / genetics
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Erythrocytes
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Erythroid Precursor Cells / cytology
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Fibroblasts
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Hematopoiesis / genetics*
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Hematopoietic Stem Cells / cytology
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Interferon Regulatory Factor-1
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Janus Kinase 2
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Leukopoiesis
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Liver / cytology
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Liver / embryology
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Mice
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Mice, Knockout
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Phenotype
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Phosphoproteins / genetics
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Protein-Tyrosine Kinases / genetics
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Protein-Tyrosine Kinases / physiology*
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Proto-Oncogene Proteins*
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RNA, Messenger / analysis
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Receptors, Cytokine / physiology*
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Receptors, Erythropoietin / physiology
Substances
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Cytokines
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DNA-Binding Proteins
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Interferon Regulatory Factor-1
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Irf1 protein, mouse
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Phosphoproteins
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Proto-Oncogene Proteins
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RNA, Messenger
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Receptors, Cytokine
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Receptors, Erythropoietin
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Protein-Tyrosine Kinases
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Jak2 protein, mouse
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Janus Kinase 2