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http://purl.uniprot.org/citations/20626616http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/20626616http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/20626616http://www.w3.org/2000/01/rdf-schema#comment"

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."xsd:string
http://purl.uniprot.org/citations/20626616http://purl.org/dc/terms/identifier"doi:10.1111/j.1538-7836.2010.03978.x"xsd:string
http://purl.uniprot.org/citations/20626616http://purl.org/dc/terms/identifier"doi:10.1111/j.1538-7836.2010.03978.x"xsd:string
http://purl.uniprot.org/citations/20626616http://purl.uniprot.org/core/author"Murphy J.W."xsd:string
http://purl.uniprot.org/citations/20626616http://purl.uniprot.org/core/author"Murphy J.W."xsd:string
http://purl.uniprot.org/citations/20626616http://purl.uniprot.org/core/author"Booth C.J."xsd:string
http://purl.uniprot.org/citations/20626616http://purl.uniprot.org/core/author"Booth C.J."xsd:string
http://purl.uniprot.org/citations/20626616http://purl.uniprot.org/core/author"Compton S.R."xsd:string
http://purl.uniprot.org/citations/20626616http://purl.uniprot.org/core/author"Compton S.R."xsd:string
http://purl.uniprot.org/citations/20626616http://purl.uniprot.org/core/author"Marks P.W."xsd:string
http://purl.uniprot.org/citations/20626616http://purl.uniprot.org/core/author"Marks P.W."xsd:string
http://purl.uniprot.org/citations/20626616http://purl.uniprot.org/core/author"Rockwell S."xsd:string
http://purl.uniprot.org/citations/20626616http://purl.uniprot.org/core/author"Rockwell S."xsd:string
http://purl.uniprot.org/citations/20626616http://purl.uniprot.org/core/author"Brooks M.B."xsd:string
http://purl.uniprot.org/citations/20626616http://purl.uniprot.org/core/author"Brooks M.B."xsd:string
http://purl.uniprot.org/citations/20626616http://purl.uniprot.org/core/author"Paidas M.J."xsd:string
http://purl.uniprot.org/citations/20626616http://purl.uniprot.org/core/author"Paidas M.J."xsd:string
http://purl.uniprot.org/citations/20626616http://purl.uniprot.org/core/author"Rinder H.M."xsd:string
http://purl.uniprot.org/citations/20626616http://purl.uniprot.org/core/author"Rinder H.M."xsd:string
http://purl.uniprot.org/citations/20626616http://purl.uniprot.org/core/author"Zelterman D."xsd:string
http://purl.uniprot.org/citations/20626616http://purl.uniprot.org/core/author"Zelterman D."xsd:string
http://purl.uniprot.org/citations/20626616http://purl.uniprot.org/core/date"2010"xsd:gYear
http://purl.uniprot.org/citations/20626616http://purl.uniprot.org/core/date"2010"xsd:gYear
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