Behavioral comparison of the C57BL/6 inbred mouse strain and their CB6F1 siblings

A large portion of basic biomedical research studies are conducted using genetically defined, inbred mouse strains. The C57BL/6 mouse strain is the most widely used genetic background in current rodent research. The rationale for using inbred strains is that all individuals are genetically identical with minimal phenotypic variation, allowing for more statistically powerful analyses. F1 hybrids between two inbred strains are also genetically identical to one another but are heterozygous at every locus at which the parental strains differ rather than homozygous. Both theoretical and empirical evidence suggests that this heterozygosity in F1 hybrids allow for potentially greater resilience in response to the inevitable stresses of laboratory environments. The purpose of this study was to characterize the differences in commonly used tests of physical performance (forelimb grip strength and rotarod) and anxiety-like behavior between the F1 hybrids created from BALB/c females mated to C57BL/6 males (called CB6F1 mice) and one of its parental strains, C57BL/6. We used a natural cross-fostering breeding scheme to minimize maternal care effects and emphasize the effects of genetic differences. We found significant correlations between anxiety-like behavioral measures and physical performance measures which are not traditionally associated with anxiety-like behavior, and which differ between strains. Findings from this study should be taken into consideration when designing behavioral studies and choosing model organisms. •CB6F1 mice have higher anxiety-like behavior than their parental strain, C57BL/6 J.•CB6F1 mice have enhanced nesting behavior compared with their parental C57BL/6 strain.•CB6F1 mice have a range of different physical capabilities than C57BL/6 mice.