Production of ES1 Plasma Carboxylesterase Knockout Mice for Toxicity Studies

• DOI: 10.1021/tx200237a
• Publication Date: 2011-08-29T16:32:37Z
• Authors: Ellen G. Duysen; Frank Koentgen; Gareth R. Williams; Christopher M. Ti...; Lawrence M. Schopfer; Douglas M. Cerasoli; Oksana Lockridge
• Keywords: Carboxylesterase; Knockout mouse

The LD50 for soman is 10–20-fold higher a mouse than human. difference in susceptibility attributed to the presence of carboxylesterase but not human plasma. Our goal was make lacking plasma carboxylesterase. We used homologous recombination inactivate ES1 gene on chromosome 8 by deleting exon 5 and introducing frame shift amino acids translated from exons 6 13. ES1–/– mice have no detectable activity normal tissues. Homozygous wild-type littermates were tested response nerve agent model compound (soman coumarin) at 3 mg/kg sc. This dose intoxicated both genotypes lethal only mice. demonstrated that protects against relatively high toxicity organophosphorus compound. should be an appropriate testing highly toxic agents evaluating protection strategies agents.