Overexpression of Human Senescence Marker Protein 30 in Mice Fails to Offer Protection Against Challenge with Organophosphorus Compounds
Technical rept. Oct 2007-Oct 2010
ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD
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To investigate the ability of human senescence marker protein 30 SMP30 to offer protection against chemical warfare nerve agents in vivo, we produced a recombinant human SMP30 fusion protein with a hemaglutinin tag expressed using an adenovirus AD-SMP30. A single intravenous injection of Ad-SMP30 into mice transduced the expression of SMP30 fusion protein in a dose and time dependant manner in the liver and diaphragm, but not in the plasma or other tissues examined in mice. Expression of SMP30 in liver and diaphragm was noted on day 2, reached peak levels on day 4 and declined thereafter. The expression levels of SMP30 achieved in the liver of Ad-SMP30 injected mice compared to the liver of mice injected with an Ad-null virus was 10- to 25-fold higher on day 4. Despite these high levels of SMP30, mice challenged with supra lethal doses of diisopropylfluorophosphate, VX or soman did not gain any discernible protection. Time to death between the control animals and animals with elevated levels of human SMP30 was not significantly different. These results suggest that wild-type human SMP30 expressed in the tissues of mice failed to offer protection against lethal levels of organophosphorus compounds in vivo.
- Chemical, Biological and Radiological Warfare