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PMID:9590174

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Citation

Neubauer, H, Cumano, A, Müller, M, Wu, H, Huffstadt, U and Pfeffer, K (1998) Jak2 deficiency defines an essential developmental checkpoint in definitive hematopoiesis. Cell 93:397-409

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.

Links

PubMed

Keywords

Anemia; Animals; B-Lymphocytes/cytology; Cytokines/pharmacology; DNA-Binding Proteins/genetics; Erythrocytes; Erythroid Precursor Cells/cytology; Fibroblasts; Hematopoiesis/genetics; Hematopoietic Stem Cells/cytology; Interferon Regulatory Factor-1; Janus Kinase 2; Leukopoiesis; Liver/cytology; Liver/embryology; Mice; Mice, Knockout; Phenotype; Phosphoproteins/genetics; Protein-Tyrosine Kinases/genetics; Protein-Tyrosine Kinases/physiology; Proto-Oncogene Proteins; RNA, Messenger/analysis; Receptors, Cytokine/physiology; Receptors, Erythropoietin/physiology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:JAK2

involved_in

GO:0007498: mesoderm development

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:JAK2

involved_in

GO:0035556: intracellular signal transduction

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

MOUSE:JAK2

involved_in

GO:0007165: signal transduction

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:JAK2

involved_in

GO:0019221: cytokine-mediated signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:JAK2

involved_in

GO:0030218: erythrocyte differentiation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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