The Jak2*V617F mice are generated by introducing a homologous mutation to the human JAK2 V617F into the mouse Jak2 gene via gene editing. This strain is homozygous lethal. Heterozygous Jak2*V617F mice exhibit classic MPN-like disease phenotypes such as splenomegaly and structural damage, significantly elevated red blood cell count, hemoglobin, hematocrit, white blood cell count, platelet count, marked megakaryocytic hyperplasia (with granulocytic and erythroid hyperplasia), extramedullary hematopoiesis, and congestion of splenic sinusoids. Therefore, Jak2*V617F mice can be used for studying the mechanisms of myeloproliferative neoplasms (MPNs) like polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), as well as for evaluating therapeutic drugs.