All (C57BL/6) Mice are not Created Equal

between the C57BL/6N and the C57BL/6C substrains (Mekada et al., 2009). Given the status of " C57BL/6 " as a standard genetic background for behavioral studies with mutants (Crawley et al., 1997), it is important to compare the substrains and describe any differences. Indeed a number of studies demonstrated significant differences between C57BL/6J and C57BL/6N on measures of ethanol preference, conditioned fear, motor coordination, and pain sensitivity (Blum et al., 1982; Bryant et al., 2008). Matsuo et al. (2010) provide a valuable extension of this earlier work by conducting a comprehensive comparison of C57BL/6J, C57BL/6N, and C57BL/6C. They achieved this in two ways: (1) with a conventional analysis of the three substrains on a battery of behavioral tasks, and (2) by taking advantage of a large data inventory the Miyakawa laboratory has accumulated in the course of studying many different mutant lines that were backcrossed onto one of the three C57BL/6 backgrounds (Takao et al., 2007). Because this laboratory employs rigorously controlled test procedures and applies a fairly consistent battery of behavioral tests to phenotype mutants, it was feasible to combine data across studies and conduct a large-scale analysis. Another plus point was that information was available on a comprehensive array of behavioral phenotypes, including measures of neu-romuscular strength, pain sensitivity, motor coordination, anxiety-like behavior, loco-motion, social interaction, startle respon-sivity, antidepressant-sensitive behaviors, and spatial working memory. Corroborating earlier work, the major finding from Matsuo et al.'s comparison was that these three substrains do indeed behave differently. Interestingly, differences were not seen across the board, but were restricted to certain phenotypes, and were especially robust for locomotor activity (relatively high in C57BL/6J), anxiety-related behaviors (lowest in C57BL/6J) and prepulse inhibition of startle (relatively high in C57BL/6N). Because all three substrains A commentary on Behavioral profiles of three C57BL/6 substrains by Matsuo, Many of the inbred mouse strains employed in behavioral neuroscience exhibit differences in phenotypes ranging from fear regulation to spatial learning to alcohol The patterns, although not always the degree, of some phenotypic variations are quite stable across time, across studies, and across laboratories (Wahlsten et al., 2006). The good news is that these strain differences offer a tractable and potentially very fruitful means to uncover genetic influences on behavior. The tougher news to swallow relates to many of the extremely powerful mutant mouse tools the field has become heavily invested in. This issue is that the genetic background of …