A novel F8 -/- rat as a translational model of human hemophilia A
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Background: In preclinical hemophilia research, an animal model that reflects both the phenotype and the pathology of the disease is needed. Objectives: Here, we describe the generation and characterization of a novel genetically engineered F8-/- rat model. Methods: The rats were produced on a Sprague Dawley background with the zinc finger nuclease technique. A founder with a 13-bp deletion in exon 16 causing a premature translational stop in the C-terminal part of the A3 domain of factor VIII was selected, and a breeding colony was established. Results: Seventy per cent of the homozygous rats had clinically manifest spontaneous hemorrhagic episodes that needed treatment. The F8-/- rats had no detectable FVIII activity, and had a significantly prolonged activated partial thromboplastin time (APTT) and clot formation time as compared with wild-type (WT)/WT rats. In vitro spiking of rat plasma with human recombinant FVIII resulted in dose-dependent normalization of the APTT. Conclusion: On the basis of the targeted deletion in F8, and the distinct physical and analytic characteristics of the rat, we conclude that an FVIII-deficient rat strain has been generated that has the potential to contribute greatly to translational research.
Originalsprog | Engelsk |
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Tidsskrift | Journal of Thrombosis and Haemostasis |
Vol/bind | 12 |
Udgave nummer | 8 |
Sider (fra-til) | 1274-1282 |
Antal sider | 9 |
ISSN | 1538-7933 |
DOI | |
Status | Udgivet - aug. 2014 |
ID: 345682769