Targeted deletion of the cytosolic domain of tissue factor in mice does not affect development

The role of the cytosolic domain of tissue factor (TT) in signal transduction and gene regulation was studied in mice with a targeted deletion of the 18 carboxyterminal intracellular amino acids. This deletion was introduced in exon 6 along with a floxed neo(R) selection cassette in intron 5 using homologous recombination in embryonic stem cells. Removal of the floxed neo(R) cassette by in vivo Cre-mediated loxP recombination yielded TF+/delta CT and TFdelta CT/delta CT mice. In contrast to TF-/- mice, TF+/delta CT and TFdelta CT/delta CT mice displayed normal embryonic development, survival, fertility, and blood coagulation. Factor VIIa or factor Xa stimulation produced similar p44/42 MAPK activation in TF+/+ and TFdelta CT/delta CT fibroblasts. These data, based on expression of a TFdelta CT molecule from the endogenous TF locus, provide conclusive proof that the cytosolic domain of TF is not essential for signal transduction in embryogenesis and in physiological postnatal processes. (C) 2001 Academic Press.