Recently, an acquired mutation of tyrosine kinase JAK2 was found in most patients with myeloproliferative disorders (MPDs) including polycythemia vera (PV), essential thrombocythemia (ET), and idiopathic myelofibrosis. We have generated transgenic mice expressing the mutation enzyme, JAK2V617F, in the hematopoietic system driven by the promoter of the vav gene. The mice are viable and fertile. One line of the transgenic mice expressed a lower level of JAK2V617F and displayed elevated blood cell counts, while the other line expressed a higher level of JAK2V617F and exhibited a marked increase in blood counts and developed phenotypes that closely resembled human ET and PV. The latter line of mice also developed marrow and spleen fibrosis as the animal aged. In general, the transgenic mice had megakaryocytic hyperplasia in the bone morrow and extramedullary hematopoiesis resulting in splenomegaly, and their serum erythropoietin level was also significantly reduced. In vitro colony assays demonstrated that transgenic mice possessed an increased number of hematopoietic progenitor cells in peripheral blood, spleen, and bone marrow and that these cells displayed hyper-sensitivity to growth factors and cytokines. The data prove that JAK2V617F is a cause of MPDs. Our study thus provides a permanent mouse system for further study to define the pathological role of JAK2V617F and to develop treatment for MPDs.
Disclosure: No relevant conflicts of interest to declare.