RGD Reference Report - A novel F8 -/- rat as a translational model of human hemophilia A. - Rat Genome Database

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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.
RGD ID: 11530071
Pubmed: PMID:24931420   (View Abstract at PubMed)
DOI: DOI:10.1111/jth.12635   (Journal Full-text)

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.



Disease Annotations    
factor VIII deficiency  (IMP,ISO)
Hemorrhage  (IDA,ISO)

Phenotype Annotations    
Objects Annotated

Genes (Rattus norvegicus)
F8  (coagulation factor VIII)
F8em1Sage  (coagulation factor VIII, procoagulant component; zinc finger nuclease induced mutant1, Sage)

Genes (Mus musculus)
F8  (coagulation factor VIII)

Genes (Homo sapiens)
F8  (coagulation factor VIII)

Strains
SD-F8em1Sage-/-/Novo  (NA)

Objects referenced in this article
Strain iNP-Npyem6Sage+/-/Iusm null Rattus norvegicus
Strain SD-F8em1Sage+/-/Novo null Rattus norvegicus
Strain SD-F8em1Sage/Novo null Rattus norvegicus

Additional Information