Hemophilia A, or Factor VIII (FVIII) deficiency, is the most common severe hereditary coagulation disorder, affecting 1 in 5000 male live births. Animal models in dog, mouse, and rabbit have been developed and used to study FVIII function and to evaluate new methods of treatment and prevention of inhibitor formation. Unfortunately, for unknown reasons, results obtained using these models didn’t always result in successful therapies when applied to humans. For new treatments to be safely and successfully translated from surrogate models to clinical trials, it is critical to develop an animal model that simultaneously and accurately parallels normal human physiology while mimicking human hemophilia’s physiopathological process. Due to its striking physiological and anatomical similarities to humans, sheep are considered an ideal model to study a vast array of pathologies. The aim of these studies was to re-establish, study, and characterize an extinct line of sheep with a spontaneous bleeding disorder that closely recapitulated human hemophilia A (
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