TARGETED DISRUPTION OF THE MOUSE FACTOR-VIII GENE PRODUCES A MODEL OF HEMOPHILIA-A

Haemophilia A is a classic X-linked disease which affects 1 in 5–10, 000 males in all populations1 and is caused by defects in coagulation factor VIII2, 3. Roughly 60% of patients have severe disease with factor VIII activity <1% of normal; they have frequent spontaneous bleeding into joints, soft tissues, muscles and internal organs. These patients usually require regular injections of plasma-derived or recombinant human factor VIII. Because this is expensive and can potentially lead to life-threatening complications, other forms of therapy, includinggene therapy, have been proposed2. Natural canine models of factor VIII and factor IX deficiency have been available for many years4–5, and gene therapy attempts on these dogs have met with partial success6–8. However, a small animal model of the disease is desirable for studies of factor VIII function and gene therapy. Using gene targeting, we have made a mouse with severe factorVIII deficiency. © 1995 Nature Publishing Group.