title: The Nbeal2(-/-) mouse as a model for the gray platelet syndrome.
abstract: The gray platelet syndrome (GPS) is a rare, autosomal-recessive platelet disorder characterized by thrombocytopenia, large platelets lacking α-granules, and variable bleeding. GPS has been linked to mutations in the neurobeachin-like 2 gene (NBEAL2). We have recently characterized Nbeal2-deficient mice and shown that the absence of Nbeal2 results in defective protein sorting in megakaryocytes (MKs) and impaired α-granule biogenesis, a finding also seen for human MKs. In the mice, the lack of α-granules results in impaired aggregation, defective platelet adhesion to collagen under flow and reduced pro-coagulant activity; findings that translate into defective hemostasis and thrombosis in vivo indicating that α-granule secretion is critical for platelet plug stability. Furthermore, we revealed a role of α-granule proteins in ischemic stroke and wound healing. Thus, Nbeal2-deficient mice recapitulate the hallmarks of human GPS without showing its phenotypic heterogeneity and are a promising model to investigate the (patho-)physiological relevancy of α-granules.
authors.affiliation: University of Würzburg; Department of Experimental Biomedicine; University Hospital and Rudolf Virchow Center; DFG Research Center for Experimental Biomedicine; Würzburg, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Deppermann
authors.affiliation: University of Würzburg; Department of Experimental Biomedicine; University Hospital and Rudolf Virchow Center; DFG Research Center for Experimental Biomedicine; Würzburg, Germany ; Plateforme Technologique et d'Innovation Biomédicale; Hôpital Xavier Arnozan; Pessac, France.
authors.forename: Paquita
authors.initials: P
authors.lastname: Nurden
authors.affiliation: Plateforme Technologique et d'Innovation Biomédicale; Hôpital Xavier Arnozan; Pessac, France.
authors.forename: Alan T
authors.initials: AT
authors.lastname: Nurden
authors.affiliation: University of Würzburg; Department of Experimental Biomedicine; University Hospital and Rudolf Virchow Center; DFG Research Center for Experimental Biomedicine; Würzburg, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Nieswandt
authors.affiliation: University of Würzburg; Department of Experimental Biomedicine; University Hospital and Rudolf Virchow Center; DFG Research Center for Experimental Biomedicine; Würzburg, Germany ; Department of Neurology; University of Würzburg; Würzburg, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Stegner
keywords: NBEAL2; gray platelet syndrome; platelet; α-granule