Behavioral responses of C57BL/6, FVB/N, and 129/SvEMS mouse strains to traumatic brain injury: implications for gene targeting approaches to neurotrauma.
Recent studies have suggested that mouse models of traumatic brain injury may be useful for evaluating the role of single gene products in brain trauma. In the present study, we report that three background strains (C57BL/6, FVB/N, and 129/SvEMS), commonly used in genetically altered mice, exhibit significantly different behavioral responses when subjected to sham surgery (n = 9 per group) or moderate controlled cortical impact (CCI) injury (n = 12 per group). Injured animals from all three strains showed delayed recovery of pedal withdrawal and righting reflexes compared to sham-operated controls. Significant deficits in both a forepaw contraflexion and rotarod task were evident for up to 7 days after injury, with no significant difference among strains. Sham-operated C57BL/6 mice performed significantly better than FVB/N and 129/SvEMS sham controls in a beam walking task up to 4 weeks after surgery. However, CCI-injured FVB/N mice outperformed injured animals from both other strains in this same task. Significant impairment of place learning in the Morris water maze and Barnes circular maze was observed at 7-10 days and 21-24 days after injury, respectively, in C57BL/6 mice when compared with sham controls. Sham-operated FVB/N and 129/SvEMS mice were unable to learn either task, and performance did not differ significantly from respective CCI injured animals. Our results suggest that background strain should be carefully considered with experiments involving genetically altered mice, especially when planning behavioral outcome measures after CNS injury.
Fox
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Georgetown Institute for Cognitive and Computational Sciences and Department of Neurology, Georgetown University Medical Center, Washington, DC 20007-2197, USA.
LeVasseur
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Faden
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D000704:Analysis of Variance; D000818:Animals; D001930:Brain Injuries / Q000235:genetics / Q000503:physiopathology* / Q000523:psychology*; D018390:Gene Targeting; D007858:Learning; D008297:Male; D018782:Maze Learning; D008568:Memory; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D009043:Motor Activity; D013028:Space Perception; D013045:Species Specificity; D013997:Time Factors