Submit Data |  Help |  Video Tutorials |  News |  Publications |  FTP Download |  REST API |  Citing RGD |  Contact   

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.

Annotation

Disease Annotations
Phenotype Annotations
Objects Annotated
Objects referenced in this article

Additional Information

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



NHLBI Logo

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