Porcine model of hemophilia A.
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| Abstract |
Hemophilia A is a common X chromosome-linked genetic bleeding disorder caused by abnormalities in the coagulation factor VIII gene (F8). Hemophilia A patients suffer from a bleeding diathesis, such as life-threatening bleeding in the brain and harmful bleeding in joints and muscles. Because it could potentially be cured by gene therapy, subhuman animal models have been sought. Current mouse hemophilia A models generated by gene targeting of the F8 have difficulties to extrapolate human disease due to differences in the coagulation and immune systems between mice and humans. Here, we generated a porcine model of hemophilia A by nuclear transfer cloning from F8-targeted fibroblasts. The hemophilia A pigs showed a severe bleeding tendency upon birth, similar to human severe hemophiliacs, but in contrast to hemophilia A mice which rarely bleed under standard breed conditions. Infusion of human factor VIII was effective in stopping bleeding and reducing the bleeding frequency of a hemophilia A piglet but was blocked by the inhibitor against human factor VIII. These data suggest that the hemophilia A pig is a severe hemophilia A animal model for studying not only hemophilia A gene therapy but also the next generation recombinant coagulation factors, such as recombinant factor VIII variants with a slower clearance rate.
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| Authors | Yuji Kashiwakura, Jun Mimuro, Akira Onishi, Masaki Iwamoto, Seiji Madoiwa, Daiichiro Fuchimoto, Shunichi Suzuki, Misae Suzuki, Shoichiro Sembon, Akira Ishiwata, Atsushi Yasumoto, Asuka Sakata, Tsukasa Ohmori, Michiko Hashimoto, Satoko Yazaki, Yoichi Sakata |
| Journal | PloS one (PLoS One) Vol. 7 Issue 11 Pg. e49450 ( 2012) ISSN: 1932-6203 [Electronic] United States |
| PMID | 23209578 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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