Generation and phenotypic analysis of protein S-deficient mice.

Détails

ID Serval
serval:BIB_116DA1E89FA4
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Generation and phenotypic analysis of protein S-deficient mice.
Périodique
Blood
Auteur(s)
Saller F., Brisset A.C., Tchaikovski S.N., Azevedo M., Chrast R., Fernández J.A., Schapira M., Hackeng T.M., Griffin J.H., Angelillo-Scherrer A.
ISSN
1528-0020[electronic]
Statut éditorial
Publié
Date de publication
2009
Volume
114
Numéro
11
Pages
2307-2314
Langue
anglais
Résumé
Protein S (PS) is an important natural anticoagulant with potentially multiple biologic functions. To investigate further the role of PS in vivo, we generated Pros(+/-) heterozygous mice. In the null (-) allele, the Pros exons 3 to 7 have been excised through conditional gene targeting. Pros(+/-) mice did not present any signs of spontaneous thrombosis and had reduced PS plasma levels and activated protein C cofactor activity in plasma coagulation and thrombin generation assays. Tissue factor pathway inhibitor cofactor activity of PS could not be demonstrated. Heterozygous Pros(+/-) mice exhibited a notable thrombotic phenotype in vivo when challenged in a tissue factor-induced thromboembolism model. No viable Pros(-/-) mice were obtained through mating of Pros(+/-) parents. Most E17.5 Pros(-/-) embryos were found dead with severe intracranial hemorrhages and most likely presented consumptive coagulopathy, as demonstrated by intravascular and interstitial fibrin deposition and an increased number of megakaryocytes in the liver, suggesting peripheral thrombocytopenia. A few E17.5 Pros(-/-) embryos had less severe phenotype, indicating that life-threatening manifestations might occur between E17.5 and the full term. Thus, similar to human phenotypes, mild heterozygous PS deficiency in mice was associated with a thrombotic phenotype, whereas total homozygous deficiency in PS was incompatible with life.
Mots-clé
Animals, Disease Models, Animal, Fetal Death/genetics, Fetal Death/metabolism, Heterozygote, Humans, Intracranial Hemorrhages/genetics, Intracranial Hemorrhages/mortality, Lipoproteins, Liver/metabolism, Liver/pathology, Megakaryocytes/metabolism, Megakaryocytes/pathology, Mice, Mice, Knockout, Protein C/genetics, Protein C/metabolism, Protein S, Protein S Deficiency/genetics, Protein S Deficiency/metabolism, Thrombin/genetics, Thrombin/metabolism, Thromboembolism/genetics, Thromboembolism/metabolism
Pubmed
Web of science
Open Access
Oui
Création de la notice
07/10/2009 16:31
Dernière modification de la notice
20/08/2019 13:39
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