RGD Reference Report - WAG-F8(m1Ycb) rats harboring a factor VIII gene mutation provide a new animal model for hemophilia A. - Rat Genome Database

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WAG-F8(m1Ycb) rats harboring a factor VIII gene mutation provide a new animal model for hemophilia A.

Authors: Booth, CJ  Brooks, MB  Rockwell, S  Murphy, JW  Rinder, HM  Zelterman, D  Paidas, MJ  Compton, SR  Marks, PW 
Citation: Booth CJ, etal., J Thromb Haemost. 2010 Nov;8(11):2472-7. doi: 10.1111/j.1538-7836.2010.03978.x.
RGD ID: 7245964
Pubmed: PMID:20626616   (View Abstract at PubMed)
DOI: DOI:10.1111/j.1538-7836.2010.03978.x   (Journal Full-text)

BACKGROUND: We recently described an inherited coagulopathy arising in an inbred colony of WAG/RijYcb rats. The bleeding phenotype, demonstrated by both male and female rats, included periarticular hemorrhage, spontaneous bruising, prolonged bleeding from minor wounds and maternal peripartum deaths. Coagulation testing of affected rats revealed normal prothrombin time but prolongation of activated partial thromboplastin time to twice that of controls. OBJECTIVE: To determine the specific coagulation factor and the underlying genetic defect responsible for the inherited coagulopathy in the WAG/RijYcb rats. RESULTS: Evaluation of individual clotting factor activities revealed that the affected animals had a specific deficiency of factor (F) VIII (FVIII). The FVIII gene (F8) has an autosomal location on chromosome 18 in rats, in contrast to its location on the X chromosome in mice and humans. Sequencing of F8 cDNA led to the identification of a point mutation resulting in a substitution, Leu176Pro, in the A1 domain, that is predicted to disrupt the tertiary structure of the FVIII molecule. Administration of human plasma or human recombinant FVIII corrects the coagulation abnormality in the affected animals. CONCLUSIONS: We have now identified the genetic basis of the hemostatic defect in the WAG/RijYcb rat colony. The larger size of rats relative to mice and the presence of this coagulation defect in both sexes provide a unique model, well-suited to the development of novel therapies for acquired and hereditary FVIII deficiencies.



Disease Annotations    

Phenotype Annotations    

Mammalian Phenotype
Objects Annotated

Genes (Rattus norvegicus)
F8  (coagulation factor VIII)
F8m1Ycb  (coagulation factor VIII, procoagulant component; mutation 1, Ycb)

Genes (Mus musculus)
F8  (coagulation factor VIII)

Genes (Homo sapiens)
F8  (coagulation factor VIII)

Strains
WAG-F8m1Ycb  (NA)


Additional Information