The biology of prothrombin.

Prothrombin and thrombin are involved in diverse biological functions. The structure of prothrombin has been studied extensively and its cDNA has been cloned from several species. The tissue-specific expression of this protein has been studied, as well as the developmental expression pattern. The structure of the human gene coding for prothrombin has been determined, and gene regulation studies have been performed that indicate that HNF-1 might be responsible for the liver-specific expression of this protein. Other regulatory elements have been identified. In order to further study the biological properties of prothrombin, prothrombin-deficient mice have been generated using gene targeting technology. Prothrombin deficiency in mice results in partial embryonic lethality. The mice that survive to birth die from bleeding events. The embryonic lethality occurs between embryonic days 9.5 and 11.5 and appears to be due to the loss of integrity of the vasculature due to a failure in blood coagulation. These results indicate that prothrombin plays not only a key role in hemostasis but suggests that it may be important for mouse development.