TARGETED DISRUPTION OF THE MURINE TISSUE FACTOR GENE RESULTS IN EMBRYONIC LETHALITY

Tissue factor (TF) is an integral membrane glycoprotein that is believ ed to be the physiologic initiator of the blood coagulation cascade, D isruption of the mouse tissue factor gene leads to embryonic lethality between days E9.5-E11.5 of gestation. On E9.5, TF(-/-) embryos appear indistinguishable from their TF(+/+) and TF(+/-) littermates. By E10. 5, TF(-/-) embryos are severely growth retarded, appear nearly bloodle ss, and are in most cases dead. Initial observations suggest that TF(- /-) embryos are dying of circulatory failure. Approximately 15% of the TF(-/-) embryos survive beyond E10.5, but none complete gestation. He terozygotes appear normal and free of bleeding complications. (C) 1996 by The American Society of Hematology.