Journal
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
Volume 12, Issue 8, Pages 1274-1282Publisher
WILEY-BLACKWELL
DOI: 10.1111/jth.12635
Keywords
animal model; gene knockout; hemophilia; phenotype; Rattus
Categories
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available