Compounds used as chemical warfare agents induce neurological damage by hampering the action of a specific enzyme, according to a study to be published in the April issue of Nature Genetics.
Organophosphates, which are used in pesticides and nerve gases, can cause immediate toxicity and death, as well as delayed damage to the nervous system-the kind that might occur in conditions like the Gulf War syndrome. Until now, it was not clear how this slower damage occurs. To address this question, Carrolee Barlow and colleagues at the Salk Institute for Biological Studies created mice lacking either one or both copies of the gene for a specific type of enzyme called neuropathy target esterase (NTE). The mice missing both copies of the gene died before birth; those missing just one copy were much more susceptible to the damaging effects of organophosphates. Thus, this study demonstrates that poisoning by organophosphates is due to a loss of NTE function. As discussed in an accompanying article by James O'Callaghan of the Centers of Disease Control and Prevention, these results do not support current theories of how organophosphates cause nerve damage. The mice lacking NTE provide a valuable model system for studying the effects of nerve gas and pesticides in mammals, and for designing therapies against organophosphate-induced damage. Author contact: Carrolee Barlow (currently at) Merck Research Laboratories San Diego, CA, USA E-mail: Carrolee_Barlow@merck.com Author of accompanying News & Views piece: James O'Callaghan Centers for Disease Control and Prevention Morgantown, WV, USA Tel: +1 304 285 6079 E-mail jdo5@cdc.gov Also available online. (C) Nature Genetics press release.
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