Correction of the coagulation defect in hemophilia A mice through factor VIII expression in skin

Steven S. Fakharzadeh, Yue Zhang, Rita Sarkar, Haig H. Kazazian

Research output: Contribution to journalArticlepeer-review

57 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)2799-2805
Number of pages7
Issue number9
StatePublished - May 1 2000
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology


Dive into the research topics of 'Correction of the coagulation defect in hemophilia A mice through factor VIII expression in skin'. Together they form a unique fingerprint.

Cite this