Low levels of tissue factor are compatible with development and hemostasis in mice

The Journal of Clinical Investigation
G C ParryN Mackman

Abstract

Tissue factor (TF) expression is associated with life-threatening thrombosis in a variety of human diseases, including sepsis, cancer, and atherosclerosis. Recently, it was shown that inactivation of the murine TF (mTF) gene results in embryonic lethality. To date, despite extensive studies on the regulation of the TF promoter in vitro, no studies have examined the cis-acting regulatory elements that control TF gene expression in vivo. Here we report that a human TF (hTF) minigene containing the human TF promoter and human TF cDNA directed a low level (approximately 1% relative to mouse TF) of both constitutive and LPS-inducible human TF expression in transgenic mice. Importantly, the human TF minigene rescued the embryonic lethality of murine TF null embryos, suggesting that human TF substituted for murine TF during embryogenesis. Rescued mice (mTF-/-, hTF+), which expressed low levels (approximately 1%) of TF activity, developed normally with no signs of a bleeding diathesis, suggesting that low TF expression can maintain hemostasis compatible with normal survival. These studies establish a novel mouse model system that can be used to examine the regulation of the human TF gene in vivo and the impact of low TF levels on the h...Continue Reading

References

Apr 1, 1992·Arteriosclerosis and Thrombosis : a Journal of Vascular Biology·N MackmanT A Drake
Aug 1, 1992·Arteriosclerosis and Thrombosis : a Journal of Vascular Biology·I K JangJ N Wilcox
Jan 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·S S TateS Udenfriend
Apr 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·J N WilcoxD Gordon
Jan 1, 1988·CRC Critical Reviews in Biochemistry·R R Bach
Nov 1, 1988·Thrombosis Research·J H MorrisseyT S Edgington
Sep 1, 1994·The Journal of Clinical Investigation·Y ZhangP P Nawroth
Sep 1, 1994·European Journal of Immunology·K M StuhlmeierF H Bach
Nov 3, 1995·The Journal of Biological Chemistry·A BierhausJ Greten
Aug 29, 1995·Proceedings of the National Academy of Sciences of the United States of America·M E BrombergA Garen
May 1, 1993·The Journal of Clinical Investigation·J D MarmurM B Taubman
May 1, 1995·Arteriosclerosis, Thrombosis, and Vascular Biology·G C Parry, N Mackman
Jan 1, 1995·British Heart Journal·E W LeathamA J Camm
Jun 25, 1996·Proceedings of the National Academy of Sciences of the United States of America·T H BuggeJ L Degen
Sep 5, 1996·Nature·P CarmelietD Collen
Apr 1, 1997·Proceedings of the National Academy of Sciences of the United States of America·T M SchlaegerT N Sato
Jun 24, 1997·Proceedings of the National Academy of Sciences of the United States of America·J R ToomeyG J Broze

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Citations

Feb 6, 2002·The Journal of Gene Medicine·Richard Saffery, K H Andy Choo
Nov 19, 2009·Clinical Reviews in Allergy & Immunology·Guillermina Girardi
Oct 27, 2004·The Veterinary Journal·Patricia A Gentry
Jun 25, 2004·The American Journal of Pathology·Laveena SharmaPeter G Tipping
Jun 26, 2003·Trends in Pharmacological Sciences·John H McVey
Dec 1, 2001·Trends in Cardiovascular Medicine·T Luther, N Mackman
Mar 13, 2012·Nature·Christoph ReinhardtFredrik Bäckhed
Feb 12, 2004·Seminars in Hematology·James Hathcock
Jul 23, 2008·Seminars in Thrombosis and Hemostasis·Rafal Pawlinski, Nigel Mackman
Mar 28, 2012·The Journal of Experimental Medicine·Marie-Luise von BrühlSteffen Massberg
May 11, 2002·Critical Care Medicine·Sagar N Doshi, Jonathan D Marmur
Aug 13, 2008·Current Opinion in Hematology·Janusz RakJoanne Yu
Feb 23, 2008·Clinical and Experimental Pharmacology & Physiology·Darren R Davis, Jonathan H Erlich
Dec 20, 2007·Journal of Thrombosis and Haemostasis : JTH·N Mackman
Jan 31, 2009·American Journal of Physiology. Gastrointestinal and Liver Physiology·James P LuyendykRuipeng Wang
Jun 12, 2010·Thrombosis and Haemostasis·A Phillip Owens, Nigel Mackman
Oct 24, 2008·Arteriosclerosis, Thrombosis, and Vascular Biology·L Vijaya Mohan Rao, Usha R Pendurthi
Dec 6, 2001·American Journal of Respiratory and Critical Care Medicine·K E Welty-WolfC A Piantadosi
Apr 26, 2003·American Journal of Respiratory and Critical Care Medicine·Martha Sue CarrawayClaude A Piantadosi
Dec 3, 2005·The Journal of Clinical Investigation·Bruce Furie, Barbara C Furie
Feb 16, 2008·The Journal of Clinical Investigation·Christoph ReinhardtBernd Engelmann
Jun 7, 2000·The Journal of Clinical Investigation·G C Parry, N Mackman
Apr 18, 2009·Anesthesia and Analgesia·Nigel Mackman
May 11, 2010·Molecular Medicine·Zhi XuFrancis J Castellino
Jul 1, 2011·Molecular Medicine·Karla C S QueirozC Arnold Spek
Oct 27, 2011·Molecular Medicine·Julia E GamboneNigel Mackman
Jun 1, 2014·PloS One·Susanna H M SlukaFelix C Tanner
Feb 4, 2014·Pathologie-biologie·R DarboussetC Dubois
Apr 27, 2001·Biochemical and Biophysical Research Communications·J MargaretoJ A Martínez
Apr 25, 2014·Thrombosis Research·Anna K Kopec, James P Luyendyk
Jul 8, 1999·Proceedings of the National Academy of Sciences of the United States of America·J ErlichN Mackman
Nov 12, 2002·Proceedings of the National Academy of Sciences of the United States of America·R PawlinskiN Mackman
Dec 3, 2014·Biochemical and Biophysical Research Communications·Nathalie MagnusJanusz Rak
Feb 16, 2016·Trends in Cardiovascular Medicine·Marco WitkowskiUrsula Rauch
Feb 7, 2016·Trends in Cardiovascular Medicine·Silvio Antoniak, Nigel Mackman
Feb 23, 2010·Thrombosis Research·Dougald M MonroeMaureane Hoffman
May 29, 2015·Journal of Atherosclerosis and Thrombosis·Kohei Tatsumi, Nigel Mackman

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