Abstract
C57BL/6 inbred strains of mice are widely used in knockout and transgenic research. To evaluate the loss-of-function and gain-of-function effects of the gene of interest, animal behaviors are often examined. However, an issue of C57BL/6 substrains that is not always appreciated is that behaviors are known to be strongly influenced by genetic background. To investigate the behavioral characteristics of C57BL/6 substrains, we subjected C57BL/6J, C57BL/6N, and C57BL/6C mice to a behavior test battery. We performed both a regular scale analysis, in which experimental conditions were tightly controlled, and large-scale analysis from large number of behavioral data that we have collected so far through the comprehensive behavioral test battery applied to 700–2,200 mice in total. Significant differences among the substrains were found in the results of various behavioral tests, including the open field, rotarod, elevated plus maze, prepulse inhibition, Porsolt forced swim, and spatial working memory version of the eight-arm radial maze. Our results show a divergence of behavioral performance in C57BL/6 substrains, which suggest that small genetic differences may have a great influence on behavioral phenotypes. Thus, the genetic background of different substrains should be carefully chosen, equated, and considered in the interpretation of mutant behavioral phenotypes.
Highlights
Remarkable advances in molecular genetics have provided powerful tools to investigate the relationships between genes and behaviors in mice
Our results show a divergence of behavioral performance in C57BL/6 substrains, which suggest that small genetic differences may have a great influence on behavioral phenotypes
The background mouse strains that were used for generating these mutant mice vary, and we have a large amount of behavioral data of control wild-type mice of different C57BL/6 substrains
Summary
Remarkable advances in molecular genetics have provided powerful tools to investigate the relationships between genes and behaviors in mice. Of the many inbred strains, C57BL/6 is the most commonly used background strain for genetically engineered mice. C57BL/6C mice were initially received from the National Cancer Institute of the NIH to the Institute of Medical Science, University of Tokyo, Japan in 1972. They were transferred to Japan SLC, Inc in 1975 and maintained for a couple of decades. Genetic analysis using SNP markers confirmed that C57BL/6C is a C57BL/6N substrain (Mekada et al, 2009). Differences in the comprehensive behavioral profiles among the three substrains have not been investigated
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