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• W2011056811 abstract "Abstract We developed 2bF9 transgenic mice in a hemophilia B mouse model with the expression of human factor IX (FIX) under control of the platelet-specific integrin αIIb promoter, to determine whether ectopically expressing FIX in megakaryocytes can enable the storage of FIX in platelet α-granules and corrects the murine hemophilia B phenotype. FIX was detected in the platelets and plasma of 2bF9 transgenic mice by both antigen and activity assays. Approximately 90% of total FIX in blood was stored in platelets, most of which is releasable on activation of platelets. Immunostaining demonstrated that FIX was expressed in platelets and megakaryocytes and stored in α-granules. All 2bF9 transgenic mice survived tail clipping, suggesting that platelet-derived FIX normalizes hemostasis in the hemophilia B mouse model. This protection can be transferred by bone marrow transplantation or platelet transfusion. However, unlike our experience with platelet FVIII, the efficacy of platelet-derived FIX was limited in the presence of anti-FIX inhibitory antibodies. These results demonstrate that releasable FIX can be expressed and stored in platelet α-granules and that platelet-derived FIX can correct the bleeding phenotype in hemophilia B mice. Our studies suggest that targeting FIX expression to platelets could be a new gene therapy strategy for hemophilia B." @default.
• W2011056811 created "2016-06-24" @default.
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• W2011056811 date "2010-08-26" @default.
• W2011056811 modified "2023-10-18" @default.
• W2011056811 title "Factor IX ectopically expressed in platelets can be stored in α-granules and corrects the phenotype of hemophilia B mice" @default.
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• W2011056811 doi "https://doi.org/10.1182/blood-2009-11-255612" @default.
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