ArticleBlood2009
Pronounced thrombocytosis in transgenic mice expressing reduced levels of Mpl in platelets and terminally differentiated megakaryocytes.
Article in Blood, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
32 citing papers in PubMed, 58 citations in OpenAlex.
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- Carica papaya ameliorates thrombocytopenia through upregulation of Interleukin-11 and modulation of thrombopoietin in mouse model of carboplatin-induced myelosuppression.Molecular biology reports · 2022Article
- Molecular Pathogenesis of Myeloproliferative Neoplasms: From Molecular Landscape to Therapeutic Implications.International journal of molecular sciences · 2022Review
- In and out: Traffic and dynamics of thrombopoietin receptor.Journal of cellular and molecular medicine · 2021Review
- The Role of Megakaryocytes in Myelofibrosis.Hematology/oncology clinics of North America · 2021Review
- The Thrombopoietin Receptor, MPL, Is a Therapeutic Target of Opportunity in the MPN.Frontiers in oncology · 2021Review
- Review
- Thrombopoietin is required for full phenotype expression in a JAK2V617F transgenic mouse model of polycythemia vera.PloS one · 2020Article
- Evaluating the Role of Janus Kinase Pathways in Platelet Homeostasis Using a Systems Modeling Approach.CPT: pharmacometrics & systems pharmacology · 2019Article
- Current Advances in Red Blood Cell Generation Using Stem Cells from Diverse Sources.Stem cells international · 2019Review
- Genetic Alterations of the Thrombopoietin/MPL/JAK2 Axis Impacting Megakaryopoiesis.Frontiers in endocrinology · 2017Review
- Identification ofFrontiers in endocrinology · 2017Article
- The Thrombopoietin Receptor: Structural Basis of Traffic and Activation by Ligand, Mutations, Agonists, and Mutated Calreticulin.Frontiers in endocrinology · 2017Review
- Recent advances in understanding myelofibrosis and essential thrombocythemia.F1000Research · 2016Review
- Cross-talk between PRMT1-mediated methylation and ubiquitylation on RBM15 controls RNA splicing.eLife · 2015Article
- Dynamin 2-dependent endocytosis is required for normal megakaryocyte development in mice.Blood · 2015Article
- Platelet studies in autism spectrum disorder patients and first-degree relatives.Molecular autism · 2015Article
- Article
- Genetic studies reveal an unexpected negative regulatory role for Jak2 in thrombopoiesis.Blood · 2014Article
- JAK2 and MPL protein levels determine TPO-induced megakaryocyte proliferation vs differentiation.Blood · 2014Article
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Authors and funding
11 authors at 5 institutions in 3 countries.
Funding
Abstract
We generated mice expressing a full-length Mpl transgene under the control of a 2-kb Mpl promoter in an Mpl(-/-) background, effectively obtaining mice that express full-length Mpl in the absence of other Mpl isoforms. These mice developed thrombocytosis with platelet levels approximately 5-fold higher than wild-type controls and markedly increased megakaryocyte numbers. The reintroduction of one wild-type Mpl allele restored normal platelet counts. We excluded the deletion of Mpl-tr, a dominant-negative isoform, as the underlying molecular cause for thrombocytosis. Instead, we found that transgene expression driven by the 2-kb Mpl promoter fragment was decreased during late megakaryocyte maturation, resulting in strongly diminished Mpl protein expression in platelets. Because platelets exert a negative feedback on thrombopoiesis by binding and consuming Tpo in the circulation through Mpl, we propose that the severe reduction of Mpl protein in platelets in Mpl-transgenic Mpl(-/-) mice shifts the equilibrium of this feedback loop, resulting in markedly elevated levels of megakaryocytes and platelets at steady state. Although the mechanism causing decreased expression of Mpl protein in platelets from patients with myeloproliferative disorders differs from this transgenic model, our results suggest that lowering Mpl protein in platelets could contribute to raising the platelet count.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.