TY - JOUR
T1 - Correction of the coagulation defect in hemophilia A mice through factor VIII expression in skin
AU - Fakharzadeh, Steven S.
AU - Zhang, Yue
AU - Sarkar, Rita
AU - Kazazian, Haig H.
PY - 2000/5/1
Y1 - 2000/5/1
N2 - To test the hypothesis that factor VIII expressed in the epidermis can correct hemophilia A, we generated transgenic mice in a factor VIII-deficient background that express human factor VIII under control of the Involucrin promoter. Mice from 5 transgenic lines had both phenotypic correction and plasma factor VIII activity. In addition to the skin, however, some factor VIII expression was detected in other tissues that have stratified squamous epithelia. To determine whether an exclusively cutaneous source of factor VIII could correct factor VIII deficiency, we grafted skin explants from transgenic mice onto mice that are double knockouts for the factor VIII and RAG-1 genes. Two graft recipients had plasma factor VIII activity of 4% to 20% of normal and improved whole blood clotting compared with factor VIII- deficient mice. Thus, expression of factor VIII from the epidermis can correct hemophilia A mice, thereby supporting the feasibility of cutaneous gene therapy for systemic disease. (C) 2000 by The American Society of Hematology.
AB - To test the hypothesis that factor VIII expressed in the epidermis can correct hemophilia A, we generated transgenic mice in a factor VIII-deficient background that express human factor VIII under control of the Involucrin promoter. Mice from 5 transgenic lines had both phenotypic correction and plasma factor VIII activity. In addition to the skin, however, some factor VIII expression was detected in other tissues that have stratified squamous epithelia. To determine whether an exclusively cutaneous source of factor VIII could correct factor VIII deficiency, we grafted skin explants from transgenic mice onto mice that are double knockouts for the factor VIII and RAG-1 genes. Two graft recipients had plasma factor VIII activity of 4% to 20% of normal and improved whole blood clotting compared with factor VIII- deficient mice. Thus, expression of factor VIII from the epidermis can correct hemophilia A mice, thereby supporting the feasibility of cutaneous gene therapy for systemic disease. (C) 2000 by The American Society of Hematology.
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U2 - 10.1182/blood.v95.9.2799.009k23_2799_2805
DO - 10.1182/blood.v95.9.2799.009k23_2799_2805
M3 - Article
C2 - 10779424
AN - SCOPUS:0034192227
SN - 0006-4971
VL - 95
SP - 2799
EP - 2805
JO - Blood
JF - Blood
IS - 9
ER -