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A novel F8 -/- rat as a translational model of human hemophilia A.

Authors: Nielsen, LN  Wiinberg, B  Hager, M  Holmberg, HL  Hansen, JJ  Roepstorff, K  Tranholm, M 
Citation: Nielsen LN, etal., J Thromb Haemost. 2014 Aug;12(8):1274-82. doi: 10.1111/jth.12635.
Pubmed: (View Article at PubMed) PMID:24931420
DOI: Full-text: DOI:10.1111/jth.12635

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.


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CRRD Object Information
CRRD ID: 11530071
Created: 2016-08-24
Species: All species
Last Modified: 2016-08-24
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.