Transgenic expression of JAK2 V617F causes myeloproliferative disorders in mice

Shu Xing, Wanting Tina Ho, Wanming Zhao, Junfeng Ma, Shaofeng Wang, Esong Xu, Qingshan Li, Xueqi Fu, Mingjiang Xu, Zhizhuang Joe Zhao

Research output: Contribution to journalArticle

136 Citations (Scopus)

Abstract

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 pheno-types 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, megakaryocyte, 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 hema topoietic 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.

Original languageEnglish (US)
Pages (from-to)5109-5117
Number of pages9
JournalBlood
Volume111
Issue number10
DOIs
StatePublished - May 15 2008
Externally publishedYes

Fingerprint

Myeloproliferative Disorders
Blood
Transgenic Mice
Essential Thrombocythemia
Polycythemia Vera
Primary Myelofibrosis
Bone
Thrombopoietin
Spleen
Erythropoietin
Hematopoietic System
Megakaryocytes
Blood Cell Count
Splenomegaly
Intercellular Signaling Peptides and Proteins
Genes
Cells
Bone Marrow Cells
Cytokines
Hyperplasia

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Xing, S., Ho, W. T., Zhao, W., Ma, J., Wang, S., Xu, E., ... Zhao, Z. J. (2008). Transgenic expression of JAK2 V617F causes myeloproliferative disorders in mice. Blood, 111(10), 5109-5117. https://doi.org/10.1182/blood-2007-05-091579

Transgenic expression of JAK2 V617F causes myeloproliferative disorders in mice. / Xing, Shu; Ho, Wanting Tina; Zhao, Wanming; Ma, Junfeng; Wang, Shaofeng; Xu, Esong; Li, Qingshan; Fu, Xueqi; Xu, Mingjiang; Zhao, Zhizhuang Joe.

In: Blood, Vol. 111, No. 10, 15.05.2008, p. 5109-5117.

Research output: Contribution to journalArticle

Xing, S, Ho, WT, Zhao, W, Ma, J, Wang, S, Xu, E, Li, Q, Fu, X, Xu, M & Zhao, ZJ 2008, 'Transgenic expression of JAK2 V617F causes myeloproliferative disorders in mice', Blood, vol. 111, no. 10, pp. 5109-5117. https://doi.org/10.1182/blood-2007-05-091579
Xing, Shu ; Ho, Wanting Tina ; Zhao, Wanming ; Ma, Junfeng ; Wang, Shaofeng ; Xu, Esong ; Li, Qingshan ; Fu, Xueqi ; Xu, Mingjiang ; Zhao, Zhizhuang Joe. / Transgenic expression of JAK2 V617F causes myeloproliferative disorders in mice. In: Blood. 2008 ; Vol. 111, No. 10. pp. 5109-5117.
@article{d4fe4a4c99204f6fbf1165d42abdcad9,
title = "Transgenic expression of JAK2 V617F causes myeloproliferative disorders in mice",
abstract = "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 pheno-types 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, megakaryocyte, 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 hema topoietic 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.",
author = "Shu Xing and Ho, {Wanting Tina} and Wanming Zhao and Junfeng Ma and Shaofeng Wang and Esong Xu and Qingshan Li and Xueqi Fu and Mingjiang Xu and Zhao, {Zhizhuang Joe}",
year = "2008",
month = "5",
day = "15",
doi = "10.1182/blood-2007-05-091579",
language = "English (US)",
volume = "111",
pages = "5109--5117",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "10",

}

TY - JOUR

T1 - Transgenic expression of JAK2 V617F causes myeloproliferative disorders in mice

AU - Xing, Shu

AU - Ho, Wanting Tina

AU - Zhao, Wanming

AU - Ma, Junfeng

AU - Wang, Shaofeng

AU - Xu, Esong

AU - Li, Qingshan

AU - Fu, Xueqi

AU - Xu, Mingjiang

AU - Zhao, Zhizhuang Joe

PY - 2008/5/15

Y1 - 2008/5/15

N2 - 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 pheno-types 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, megakaryocyte, 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 hema topoietic 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.

AB - 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 pheno-types 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, megakaryocyte, 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 hema topoietic 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.

UR - http://www.scopus.com/inward/record.url?scp=46749137278&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=46749137278&partnerID=8YFLogxK

U2 - 10.1182/blood-2007-05-091579

DO - 10.1182/blood-2007-05-091579

M3 - Article

C2 - 18334677

AN - SCOPUS:46749137278

VL - 111

SP - 5109

EP - 5117

JO - Blood

JF - Blood

SN - 0006-4971

IS - 10

ER -