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

Journal of Thrombosis and Haemostasis : JTH
C J BoothP W Marks

Abstract

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. To determine the specific coagulation factor and the underlying genetic defect responsible for the inherited coagulopathy in the WAG/RijYcb rats. 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. We have now identified the genetic basis of the hemosta...Continue Reading

References

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Citations

Apr 11, 2014·Iranian Red Crescent Medical Journal·Habib OnsoriAbbas Ali Hosseinpour Feizi
Jan 22, 2011·Journal of Thrombosis and Haemostasis : JTH·P E Monahan
Aug 21, 2013·Seminars in Hematology·Jay N Lozier, Timothy C Nichols
Oct 22, 2016·Thrombosis Journal·Ching-Tzu YenShu-Wha Lin
Jun 17, 2014·Journal of Thrombosis and Haemostasis : JTH·L N NielsenM Tranholm
Nov 21, 2015·Journal of Thrombosis and Haemostasis : JTH·B N ChaoM J Lenardo
Dec 15, 2020·Molecular Therapy. Methods & Clinical Development·Wenjing CaoWeidong Xiao

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