edoc

JAK2 exon 12 mutant mice display isolated erythrocytosis and changes in iron metabolism favoring increased erythropoiesis

Grisouard, Jean and Li, Sai and Kubovcakova, Lucia and Rao, Tata Nageswara and Meyer, Sara C. and Lundberg, Pontus and Hao-Shen, Hui and Romanet, Vincent and Murakami, Masato and Radimerski, Thomas and Dirnhofer, Stephan and Skoda, Radek C.. (2016) JAK2 exon 12 mutant mice display isolated erythrocytosis and changes in iron metabolism favoring increased erythropoiesis. Blood, 128 (6). pp. 839-851.

Full text not available from this repository.

Official URL: https://edoc.unibas.ch/62359/

Downloads: Statistics Overview

Abstract

Mutations in JAK2 exon 12 are frequently found in patients with polycythemia vera (PV) that do not carry a JAK2-V617F mutation. The majority of these patients display isolated erythrocytosis. We generated a mouse model that expresses JAK2-N542-E543del, the most frequent JAK2 exon 12 mutation found in PV patients. Mice expressing the human JAK2-N542-E543del (Ex12) showed a strong increase in red blood cell parameters but normal neutrophil and platelet counts, and reduced overall survival. Erythropoiesis was increased in the bone marrow and spleen, with normal megakaryopoiesis and absence of myelofibrosis in histopathology. Erythroid progenitors and precursors were increased in hematopoietic tissues, but the numbers of megakaryocytic precursors were unchanged. Phosphorylation Stat3 and Erk1/2 proteins were increased, and a trend toward increased phospho-Stat5 and phospho-Stat1 was noted. However, Stat1 knock out in Ex12 mice induced no changes in platelet or red cell parameters, indicating that Stat1 does not play a central role in mediating the effects of Ex12 signaling on megakaryopoiesis or erythropoiesis. Ex12 mice showed decreased expression of hepcidin and increased expression of transferrin receptor-1 and erythroferrone, suggesting that the strong erythroid phenotype in Ex12 mutant mice is favored by changes in iron metabolism that optimize iron availability to allow maximal production of red cells.
Faculties and Departments:03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Hämatologie > Molekulare Medizin (Skoda)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Hämatologie > Molekulare Medizin (Skoda)
03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Experimental Hematology (Skoda)
03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Myeloid Malignancies (Meyer S)
UniBasel Contributors:Meyer, Sara C. and Skoda, Radek C.
Item Type:Article, refereed
Article Subtype:Research Article
ISSN:1528-0020 (Electronic)0006-4971 (Linking)
Note:Publication type according to Uni Basel Research Database: Journal article
Related URLs:
Identification Number:
Last Modified:05 Jan 2019 11:53
Deposited On:05 Jan 2019 11:53

Repository Staff Only: item control page