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Hemostatic and hematological abnormalities in gain‐of‐function fps / fes transgenic mice are associated with the angiogenic phenotype
Author(s) -
Sangrar W.,
Senis Y.,
Samis J. A.,
Gao Y.,
Richardson M.,
Lee D. H.,
Greer P. A.
Publication year - 2004
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/j.1538-7836.2004.00956.x
Subject(s) - phenotype , transgene , gain of function , genetically modified mouse , function (biology) , cancer research , medicine , pathology , immunology , biology , microbiology and biotechnology , gene , genetics
Summary. 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.