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Construction and validation of a mouse model of Myeloproliferative Neoplasms

• 1、School of biomedical sciences Hunan University

Abstract：Objective: To establish a hematopoietic system-specific JAK2V617F mutant mouse model for investigating the pathological role of this mutation in myeloproliferative neoplasms (MPN) and to provide an experimental tool for elucidating the JAK2-STAT5 signaling pathway mechanism and advancing therapeutic strategies.Methods: JAK2fl/+ mice carrying LoxP sites were crossed with Vav-Cre mice using gene-editing technology to generate heterozygous mice (JAK2VF/+) with hematopoietic-restricted JAK2V617F expression. Genotyping was validated via polymerase chain reaction (PCR) amplification. Peripheral blood parameters, including red blood cell counts, hemoglobin levels, and hematocrit, were analyzed by complete blood count (CBC) to assess hyperproliferativephenotypes.Results: Genotyping confirmed successful retention of the mutant exon 14 in JAK2VF/+ mice. Peripheral blood analysis demonstrated significant increases in red blood cell counts, hemoglobin levels, and hematocrit, consistent with the hyperproliferative phenotype observed in MPN. Homozygous mutation (JAK2VF/VF) caused embryonic lethality, restricting the study to heterozygous mice.Conclusion: The JAK2V617F conditional mutant mouse model recapitulates MPN pathological features, confirming that hematopoietic-specific JAK2V617F mutation drives abnormal hematopoiesis. This model serves as a vital experimental platform for exploring MPN pathogenesis and developing targeted therapies.

Keywords： Molecular Genetics Myeloproliferative neoplasms JAK2V617F mutation mice