Targeted deletion of the cytosolic domain of tissue factor in mice does not affect development
E Melis, L Moons, M De Mol, JM Herbert… - Biochemical and …, 2001 - Elsevier
E Melis, L Moons, M De Mol, JM Herbert, N Mackman, D Collen, P Carmeliet, M Dewerchin
Biochemical and biophysical research communications, 2001•ElsevierThe role of the cytosolic domain of tissue factor (TF) in signal transduction and gene
regulation was studied in mice with a targeted deletion of the 18 carboxy-terminal
intracellular amino acids. This deletion was introduced in exon 6 along with a floxed neoR
selection cassette in intron 5 using homologous recombination in embryonic stem cells.
Removal of the floxed neoR cassette by in vivo Cre-mediated loxP recombination yielded
TF+/δCT and TFδCT/δCT mice. In contrast to TF−/− mice, TF+/δCT and TFδCT/δCT mice …
regulation was studied in mice with a targeted deletion of the 18 carboxy-terminal
intracellular amino acids. This deletion was introduced in exon 6 along with a floxed neoR
selection cassette in intron 5 using homologous recombination in embryonic stem cells.
Removal of the floxed neoR cassette by in vivo Cre-mediated loxP recombination yielded
TF+/δCT and TFδCT/δCT mice. In contrast to TF−/− mice, TF+/δCT and TFδCT/δCT mice …
The role of the cytosolic domain of tissue factor (TF) in signal transduction and gene regulation was studied in mice with a targeted deletion of the 18 carboxy-terminal intracellular amino acids. This deletion was introduced in exon 6 along with a floxed neoR selection cassette in intron 5 using homologous recombination in embryonic stem cells. Removal of the floxed neoR cassette by in vivo Cre-mediated loxP recombination yielded TF+/δCT and TFδCT/δCT mice. In contrast to TF−/− mice, TF+/δCT and TFδCT/δCT 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 TFδCT/δCT fibroblasts. These data, based on expression of a TFδCT 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.
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