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Open AccessArticle

Comparison of Neurological Function in Males and Females from Two Substrains of C57BL/6 Mice

Department of Biological Sciences, Northern Kentucky University, SC344 Nunn Dr, Highland Heights, KY 41099, USA
Department of Psychological Science, Northern Kentucky University, MP 359 Nunn Dr, Highland Heights, KY 41099, USA
Division of Neurology, Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, 3333 Burnett Avenue, Cincinnati, OH 45229, USA
The Royal (Dick) School of Veterinary Studies, the University of Edinburgh, Edinburgh EH25 9RG, UK
Author to whom correspondence should be addressed.
Academic Editor: David Wallace
Toxics 2015, 3(1), 1-17;
Received: 12 June 2014 / Accepted: 17 December 2014 / Published: 25 December 2014
(This article belongs to the Special Issue Developmental Neurotoxicology)
The C57BL/6 (B6) mouse is the background strain most frequently used for genetically-modified mice. Previous studies have found significant behavioral and genetic differences between the B6J (The Jackson Laboratory) and B6N substrains (National Institutes of Health); however, most studies employed only male mice. We performed a comprehensive battery of motor function and learning and memory tests on male and female mice from both substrains. The B6N male mice had greater improvement in the rotarod test. In contrast, B6J female mice had longer latencies to falling from the rotarod. In the Morris water maze (MWM), B6J males had significantly shorter latencies to finding the hidden platform. However, B6N females had significantly shorter path lengths in the reversal and shifted-reduced phases. In open field locomotor activity, B6J males had higher activity levels, whereas B6N females took longer to habituate. In the fear conditioning test, B6N males had a significantly longer time freezing in the new context compared with B6J males, but no significant differences were found in contextual or cued tests. In summary, our findings demonstrate the importance of testing both males and females in neurobehavioral studies. Both factors (sex and substrain) must be taken into account when designing developmental neurotoxicology studies. View Full-Text
Keywords: C57BL/6; substrain; sex differences; behavior; neurobiology; genetics C57BL/6; substrain; sex differences; behavior; neurobiology; genetics
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Ashworth, A.; Bardgett, M.E.; Fowler, J.; Garber, H.; Griffith, M.; Curran, C.P. Comparison of Neurological Function in Males and Females from Two Substrains of C57BL/6 Mice. Toxics 2015, 3, 1-17.

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