Gene targeting in hemostasis. Prothrombin

There have been extensive studies on the structure and function of prothrom bin; a protein critical for the coagulation of blood. The biological functi ons of prothrombin and its activated form, thrombin are discussed, as well as the structure and functional domains of the protein. Prothrombin is expr essed in a tissue-specific manner and its gene structure and regulatory ele ments have been analyzed in detail. In order to learn more about the functi ons of prothrombin in an in vivo context, the gene was ablated in mice. Hom ozygous deletion of prothrombin results in a partial embryonic lethal pheno type. Approximately half of the homozygous mutant mice die during mid-gesta tion and the remainder die soon after birth. The cause of death of neonates is due to excessive bleeding, while null embryos have a lack of integrity of the yolk sac membrane resulting in bleeding into the yolk sac cavity. Th ese results are discussed in relation to the phenotypes found for other mic e lacking specific coagulation factors.