Jak2 deficiency defines an essential developmental checkpoint in definitive hematopoiesis.
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.
Neubauer
H
H
Institute of Medical Microbiology, Immunology, and Hygiene, Technical University of Munich, Germany.
Cumano
A
A
Müller
M
M
Wu
H
H
Huffstadt
U
U
Pfeffer
K
K
D000740:Anemia; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology; D016207:Cytokines / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000235:genetics; D004912:Erythrocytes; D015672:Erythroid Precursor Cells / Q000166:cytology; D005347:Fibroblasts; D006410:Hematopoiesis / Q000235:genetics*; D006412:Hematopoietic Stem Cells / Q000166:cytology; D050856:Interferon Regulatory Factor-1; D053614:Janus Kinase 2; D019891:Leukopoiesis; D008099:Liver / Q000166:cytology / Q000196:embryology; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D010750:Phosphoproteins / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000502:physiology*; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger / Q000032:analysis; D018121:Receptors, Cytokine / Q000502:physiology*; D017467:Receptors, Erythropoietin / Q000502:physiology
D016207:Cytokines; D004268:DNA-Binding Proteins; D050856:Interferon Regulatory Factor-1; C494258:Irf1 protein, mouse; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D018121:Receptors, Cytokine; D017467:Receptors, Erythropoietin; D011505:Protein-Tyrosine Kinases; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2