Correction of the coagulation defect in hemophilia A mice through factor VIII expression in skin.
نویسندگان
چکیده
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. (Blood. 2000;95:2799-2805)
منابع مشابه
The Effects of Novel Mutations in A1 Domain of Human Coagulation Factor VIII on Its Secretion Level in Cultured Mammalian Cells
Inefficient secretion of the human coagulation factor (hFVIII) in mammalian expression systems is one ofthe main causes of the hFVIII low expression level, attributed to its interaction with a chaperone known asBiP/GRP78. In order to improve secretion efficiency of the hFVIII, based on the higher secretion level of theporcine FVIII and analysis of the hFVIII A110 region, that ...
متن کاملCoagulation Therapy in Hemophilia A and its Relation to Factor VIII Inhibitor in Northeast of Iran
متن کامل
Clinical and Laboratory Approaches to Hemophilia A
Hemophilia A is a worldwide disorder of coagulation system. It is a male disorder, yet females with hemophilia are rarely seen in communities with high rate of consanguineous marriages. The abnormalities in factor VIII gene transfer as an X-linked pattern in the family, affects as many as one-third of patients who had no family history of abnormality and thus the occurrence of a sporadic mutati...
متن کاملThe Current Status of Bone Marrow Transplantation in Treatment of Patients with Hemophilia
Background Bone marrow transplantation (BMT)is nowadays used in various hematological disorders including leukemias. Hemophilia A & B are sex linked bleeding disorders in which there are various genetic abnormalities in factor VIII & IX genes. Among various hematological disorders, bleeding disorders mainly hemophilia in now widely treated using plasma derived and recombinant factor VIII & IX ...
متن کاملThe Survey of Effective Agents on Factor VIII and IX Inhibitors in Patients with Hemophilia A and B in Kermanshah Province
Background: Hemophilia is the most frequent severe hereditary hemorrhagic disease due to deficiency of coagulation factors VIII (Hemophilia A) or IX (Hemophilia B) in plasma. We aimed to identify patients with hemophilia in Kermanshah, Iran and assess the incidence of inhibitors in this population and its associated factors. Methods: This study was conducted on patients with hemophilia...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Blood
دوره 95 9 شماره
صفحات -
تاریخ انتشار 2000