NDLI: Factor IX ectopically expressed in platelets can be stored in α-granules and corrects the phenotype of hemophilia B mice

Content Provider	PubMed Central
Author	Zhang, Guowei Shi, Qizhen Fahs, Scot A. Kuether, Erin L. Walsh, Christopher E. Montgomery, Robert R.
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.
Related Links	http://dx.doi.org/10.1182/blood-2009-11-255612
Ending Page	1243
Page Count	9
Starting Page	1235
File Format	PDF
ISSN	00064971
e-ISSN	15280020
Journal	Blood
Issue Number	8
Volume Number	116
Language	English
Publisher	American Society of Hematology
Publisher Date	2010-08-26
Access Restriction	Open
Rights Holder	American Society of Hematology
Subject Keyword	Immunology Cell Biology Biochemistry Hematology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cell Biology Hematology Biochemistry Immunology

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