[Frontiers in Bioscience 6, d98-104, February 1, 2001]
GENE TARGETING IN HEMOSTASIS. FACTOR VII
W.M. Keck Center for Transgene Research and the Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, USA
TABLE OF CONTENTS
1. Abstract
2. The role of Factor VII in coagulation
3. Protein biochemistry
4. Human FVII deficiency
5. Targeting of the FVII gene in mice
6. Phenotypic characterization of FVII-/- neonates
7. Phenotypic characterization of FVII-/- embryos
8. Potential functions of FVII/TF outside of hemostasis
9. Human clinical data and the selection of potential in vivo mutations in mice
10. Perspective
11. Acknowledgments
12. References
1. ABSTRACT
Factor VII (FVII), in concert with its natural cofactor and receptor, Tissue Factor (TF), initiates the process of blood coagulation following vascular injury. Mice completely deficient in FVII were generated via specific deletion of exons 2 to 8, thus deleting the entire coding region of the mature protein. In contrast to the early lethality observed in TF-deficient embryos (TF-/-), embryos deficient in FVII (FVII-/-) developed normally, without incidence of hemorrhage. However, FVII-/- neonates succumbed to either early intraabdominal or intracranial hemorrhage in later life.