ABSTRACT
INTRODUCTION The advent of gene targeting technology has made it feasible to alter, in a precisely controlled f ashion, the function of specific genes in complex model organisms such as laboratory mice. Gene targeting allows the achievement of a complete loss (or ‘knockout’) of gene function, and the study of the physiological consequences of the mutation in an intact animal. Over the past decade, the gene knock-out approach has been used in mice to ablate the genes for almost all currently known coagulation factors, fibrinolytic enzymes, and regulators of coagulation and fibrinolysis, resulting in a generation of knockout mice with precisely defined defects in the hemostatic mechanism. Such a complete absence of function and antigen expression is extremely rare in humansor, as is the case for most factors, has not been observed at all. Many genetically altered mice constitute animal models for hemostatic disorders associated with bleeding or thrombosis.
