Behavioral Characterization of GCLM-Knockout Mice, a Model for Enhanced Susceptibility to Oxidative Stress
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-kno...
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| Format: | Article |
| Language: | English |
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Wiley
2011-01-01
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| Series: | Journal of Toxicology |
| Online Access: | http://dx.doi.org/10.1155/2011/157687 |
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| author | Toby B. Cole Gennaro Giordano Aila L. Co Isaac Mohar Terrance J. Kavanagh Lucio G. Costa |
| author_facet | Toby B. Cole Gennaro Giordano Aila L. Co Isaac Mohar Terrance J. Kavanagh Lucio G. Costa |
| author_sort | Toby B. Cole |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-e51606aff8ff457d990cc4c001ff6216 |
| institution | Kabale University |
| issn | 1687-8191 1687-8205 |
| language | English |
| publishDate | 2011-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Toxicology |
| spelling | doaj-art-e51606aff8ff457d990cc4c001ff62162025-08-20T03:26:20ZengWileyJournal of Toxicology1687-81911687-82052011-01-01201110.1155/2011/157687157687Behavioral Characterization of GCLM-Knockout Mice, a Model for Enhanced Susceptibility to Oxidative StressToby B. Cole0Gennaro Giordano1Aila L. Co2Isaac Mohar3Terrance J. Kavanagh4Lucio G. Costa5Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98195, USADepartment of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98195, USADivision of Medical Genetics, University of Washington, Seattle, WA 98195, USADepartment of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98195, USADepartment of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98195, USADepartment of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98195, USAGlutathione (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.http://dx.doi.org/10.1155/2011/157687 |
| spellingShingle | Toby B. Cole Gennaro Giordano Aila L. Co Isaac Mohar Terrance J. Kavanagh Lucio G. Costa Behavioral Characterization of GCLM-Knockout Mice, a Model for Enhanced Susceptibility to Oxidative Stress Journal of Toxicology |
| title | Behavioral Characterization of GCLM-Knockout Mice, a Model for Enhanced Susceptibility to Oxidative Stress |
| title_full | Behavioral Characterization of GCLM-Knockout Mice, a Model for Enhanced Susceptibility to Oxidative Stress |
| title_fullStr | Behavioral Characterization of GCLM-Knockout Mice, a Model for Enhanced Susceptibility to Oxidative Stress |
| title_full_unstemmed | Behavioral Characterization of GCLM-Knockout Mice, a Model for Enhanced Susceptibility to Oxidative Stress |
| title_short | Behavioral Characterization of GCLM-Knockout Mice, a Model for Enhanced Susceptibility to Oxidative Stress |
| title_sort | behavioral characterization of gclm knockout mice a model for enhanced susceptibility to oxidative stress |
| url | http://dx.doi.org/10.1155/2011/157687 |
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