The DOI matches its Crossref record; 37 of the 37 references it cites were found in a registry or an index.
Ratio of mutant JAK2-V617F to wild-type Jak2 determines the MPD phenotypes in transgenic mice
Open accessAbstract
An acquired somatic mutation in the JAK2 gene (JAK2-V617F) is present in the majority of patients with myeloproliferative disorders (MPDs). Several phenotypic manifestations (polycythemia vera [PV], essential thrombocythemia [ET], and primary myelofibrosis) can be associated with the same mutation. We generated JAK2-V617F transgenic mice using a human JAK2 gene with the sequences encoding the kinase domain placed in the inverse orientation and flanked by antiparallel loxP sites. Crossing mice of one transgenic line (FF1) with transgenic mice expressing Cre-recombinase under the control of the hematopoiesis specific Vav promoter led to expression of JAK2-V617F that was lower than the endogenous wild-type Jak2. These mice developed a phenotype resembling ET with strongly elevated platelet counts and moderate neutrophilia. Induction of the JAK2-V617F transgene with the interferon-inducible MxCre resulted in expression of JAK2-V617F approximately equal to wild-type Jak2 and a PV-like phenotype with increased hemoglobin, thrombocytosis, and neutrophilia. Higher levels of JAK2-V617F in mouse bone marrow by retroviral transduction caused a PV-like phenotype without thrombocytosis. These data are consistent with the hypothesis that the ratio of mutant to wild-type JAK2 is critical for the phenotypic manifestation. A similar correlation was also found in patients with MPD.
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Cites
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Cited by
Mechanisms and consequences of Jak–STAT signaling in the immune system
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Genetic basis and molecular pathophysiology of classical myeloproliferative neoplasms
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JAK/STAT signaling in hematological malignancies
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Neuropathy of haematopoietic stem cell niche is essential for myeloproliferative neoplasms
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Metadata
- Authors
- Tiedt, R., Hao-Shen, H., Sobas, M. A., Looser, R., Dirnhofer, S., Schwaller, J., & Skoda, R. C.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2008-04-15
- Volume
- 111
- Issue
- 8
- Pages
- 3931-3940
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2038195476
- Cited by
- 440
- References
- 37
- FWCI
- 17.63
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Tiedt, R., Hao-Shen, H., Sobas, M. A., Looser, R., Dirnhofer, S., Schwaller, J., & Skoda, R. C. (2008). Ratio of mutant JAK2-V617F to wild-type Jak2 determines the MPD phenotypes in transgenic mice. Blood. https://doi.org/10.1182/blood-2007-08-107748
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
