Characterization of Genetically Modified Mice as Improved Animal Models for Organophosphorus Nerve Agent Research
Abstract
Miceand other small rodent animal models are known to have greater resistance tointoxication by the organophosphorus (OP) nerve agents sarin, soman, andcyclosarin than do humans and non‐human primates. This resistance has beendirectly attributed to the presence of carboxylesterase in the blood plasma of these animals. Carboxylesterase acts asan endogenous bioscavenger and is not found in the blood plasma of humans andnon‐human primates. To create an improved small animal model of nerve agentintoxication, the gene encoding serum carboxylesterase (Es1) in C57BL/6 mice was deleted to generate a transgenic strain of mice (Es1 KO) that no longer expresses this protein. In contrast with previousgenetic modification efforts to remove other endogenous bioscavenger enzymes frommice, the median lethal dose for several OP nerve agents in Es1 KO mice was significantly lower than that in wild type control mice. Physiological and behavioral characterizations of these mice have been conducted in an effort to determine their suitability as a small animal model for OP nerve agentintoxication.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Apr 01, 2018
- Source ID
- 10.1096/fasebj.2018.32.1_supplement.lb67
Entities
People
- C Linn Cadieux
- Douglas M. Cerasoli
- Emily N. Dunn
- Erik M Matson
- John H. McDonough
- Keith S.l. Morgan
- Sandra J DeBus
Organizations
- Defense Threat Reduction Agency
- United States Army Medical Research Institute of Chemical Defense