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Journal of Toxicology
Volume 2011, Article ID 157687, 7 pages
Research Article

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

1Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98195, USA
2Division of Medical Genetics, University of Washington, Seattle, WA 98195, USA
3Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA
4Department of Human Anatomy, Pharmacology and Forensic Science, University of Parma Medical School, 43121 Parma, Italy

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-type mice. Tests included the rotarod, acoustic startle reflex and prepulse inhibition of the startle reflex, open field behavior, and the platform reversal variant of the Morris Water Maze. Results showed no differences between Gclm−/− and wild-type mice in any of the neurobehavioral tests. However, more subtle alterations, or changes which may appear as animals age, cannot be excluded.