Transgenic expression of JAK2V617F causes myeloproliferative disorders in mice.
The JAK2(V617F) mutation was found in most patients with myeloproliferative disorders (MPDs), including polycythemia vera, essential thrombocythemia, and primary myelofibrosis. We have generated transgenic mice expressing the mutated enzyme in the hematopoietic system driven by a vav gene promoter. The mice are viable and fertile. One line of the transgenic mice, which expressed a lower level of JAK2(V617F), showed moderate elevations of blood cell counts, whereas another line with a higher level of JAK2(V617F) expression displayed marked increases in blood counts and developed phenotypes that closely resembled human essential thrombocythemia and polycythemia vera. The latter line of mice also developed primary myelofibrosis-like symptoms as they aged. The transgenic mice showed erythroid, megakaryocytic, and granulocytic hyperplasia in the bone marrow and spleen, displayed splenomegaly, and had reduced levels of plasma erythropoietin and thrombopoietin. They possessed an increased number of hematopoietic progenitor cells in peripheral blood, spleen, and bone marrow, and these cells formed autonomous colonies in the absence of growth factors and cytokines. The data show that JAK2(V617F) can cause MPDs in mice. Our study thus provides a mouse model to study the pathologic role of JAK2(V617F) and to develop treatment for MPDs.
Xing
Shu
S
Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, USA.
Wanting
Tina Ho
TH
Zhao
Wanming
W
Ma
Junfeng
J
Wang
Shaofeng
S
Xu
Xuesong
X
Li
Qingshan
Q
Fu
Xueqi
X
Xu
Mingjiang
M
Zhao
Zhizhuang Joe
ZJ
D000818:Animals; D004921:Erythropoietin / Q000032:analysis; D006412:Hematopoietic Stem Cells; D006965:Hyperplasia; D053614:Janus Kinase 2 / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D020125:Mutation, Missense; D009196:Myeloproliferative Disorders / Q000209:etiology / Q000235:genetics*; D010641:Phenotype; D013926:Thrombopoietin / Q000032:analysis; D019076:Transgenes
D004921:Erythropoietin; D013926:Thrombopoietin; D053614:Janus Kinase 2