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Hemostatic and hematological abnormalities in gain-of-function fps/fes transgenic mice are associated with the angiogenic phenotype.
- Source :
-
Journal of thrombosis and haemostasis : JTH [J Thromb Haemost] 2004 Nov; Vol. 2 (11), pp. 2009-19. - Publication Year :
- 2004
-
Abstract
- The Fps/Fes tyrosine kinase has been implicated in the regulation of hematopoiesis and inflammation. Mice expressing an activated variant of Fps/Fes (MFps) encoded by a gain-of-function mutant transgenic fps/fes allele (fps(MF)) exhibited hematological phenotypes, which suggested that Fps/Fes can direct hematopoietic lineage output. These mice also displayed marked hypervascularity and multifocal-hemangiomas which implicated this kinase in the regulation of angiogenesis. Here we explored the potential involvement of Fps/Fes in the regulation of hemostasis through effects on blood cells and the vascular endothelium. Hematological parameters of fps(MF) mice were characterized by peripheral blood analysis, histology, and transmission electron microscopy. Hemostasis parameters and platelet functions were assessed by flow cytometry and measurements of activated partial thromboplastin time, prothrombin time, thrombin clot time, platelet aggregation, bleeding times and in vitro fibrinolytic assays. Hematological and morphological analyses showed that fps(MF) mice displayed mild thrombocytopenia, anemia, red cell abnormalities and numerous hemostatic defects, including hypofibrinogenemia, hyper-fibrinolysis, impaired whole blood aggregation and a mild bleeding diathesis. fps(MF) mice displayed a complex array of hemostatic perturbations which are reminiscent of hemostatic disorders such as disseminated intravascular coagulation (DIC) and of hemangioma-associated pathologies such as Kasabach-Merritt phenomenon (KMS). These studies suggest that Fps/Fes influences both angiogenic and hemostatic function through regulatory effects on the endothelium.
- Subjects :
- Anemia etiology
Animals
Blood Coagulation Disorders etiology
Blood Platelets pathology
Endothelium, Vascular pathology
Hemolysis
Mice
Mice, Transgenic
P-Selectin analysis
Phenotype
Protein-Tyrosine Kinases genetics
Proto-Oncogene Proteins genetics
Proto-Oncogene Proteins c-fes
Thrombocytopenia etiology
Thrombopoiesis
Hemostasis
Neovascularization, Physiologic
Protein-Tyrosine Kinases deficiency
Protein-Tyrosine Kinases physiology
Proto-Oncogene Proteins deficiency
Proto-Oncogene Proteins physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1538-7933
- Volume :
- 2
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Journal of thrombosis and haemostasis : JTH
- Publication Type :
- Academic Journal
- Accession number :
- 15550033
- Full Text :
- https://doi.org/10.1111/j.1538-7836.2004.00956.x