Behavioral Characterization of GCLM-Knockout Mice, a Model for Enhanced Susceptibility to Oxidative Stress.pdfVIP

Hindawi Publishing Corporation Journal of Toxicology Volume 2011, Article ID 157687, 7 pages doi:10.1155/2011/157687 Research Article Behavioral Characterization of GCLM -Knockout Mice, a Model for Enhanced Susceptibility to Oxidative Stress Toby B. Cole,1, 2, 3 Gennaro Giordano,1 Aila L. Co,2, 3 Isaac Mohar,1 Terrance J. Kavanagh,1 and Lucio G. Costa1, 4 1 Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98195, USA 2 Division of Medical Genetics, University of Washington, Seattle, WA 98195, USA 3 Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA 4 Department of Human Anatomy, Pharmacology and Forensic Science, University of Parma Medical School, 43121 Parma, Italy Correspondence should be addressed to Lucio G. Costa, lgcosta@ Received 20 November 2010; Accepted 25 February 2011 Academic Editor: M. Teresa Colomina Fosch Copyright © 2011 Toby B. Cole et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Glutathione (GSH) is a major player in cellular defense against oxidative stress. Deletion of the modifier subunit of glutamate cysteine ligase (GCLM), the first and the rate-limiting enzyme in the synthesis of GSH, leads to significantly lower GSH levels in all tissues including the brain. GCLM-knockout (Gclm−/ − ) mice may thus represent a model for compromised response to oxidative stress amenable to in vitro and in vivo investigations. In order to determine whether the diminished GSH content would by itself cause behavioral alterations, a series of behavioral tests were carried out comparing young adult Gclm−/ − with wild-ty