Contrasting phenotypes of C57BL/6JOlaHsd, 129S2/SvHsd and 129/SvEv mice in two exploration-based tests of anxiety-related behaviour

Abstract

Knockout mice are typically generated on a mixed genetic background and, as such, detailed behavioural characterisation of these background strains is essential to the valid interpretation of mutant phenotypes. In this context, recent research has revealed significant differences in anxiety-like behaviour among the most commonly used background strains (C57BL/6J and various 129 substrains), leading to the possibility that at least certain mutant phenotypes may not after all be due to the targeted mutation. However, these findings derive largely from behavioural test batteries in which there may well be an experiential confound, while the widely reported hypolocomotor profile of most 129 substrains may compromise the principal indices of anxiety-like behaviour. In the present study, we have compared the behavioural profiles of three commonly used background strains (C57BL/6JOlaHsd, 129/SvEv and 129S2/SvHsd) in two of the most popular animal models of anxiety—the elevated plus-maze (EPM) and light/dark exploration (LDE) tests. Naive animals were used for each procedure, ethological scoring methods were employed throughout, and the inbred phenotypes were also compared with that of an outbred strain (Swiss–Webster) widely employed in test validation and behavioural pharmacology. Our results show that, despite their hypolocomotor profile, both 129 substrains display higher levels of anxiety-like behaviour (conventional and/or ethological measures) relative to the C57BL/6JOlaHsd strain. Furthermore, all three inbred strains were less active in both tests when compared with the outbred Swiss–Webster strain. However, whereas C57BL/6JOlaHsd mice displayed lower levels of anxiety-like behaviour than their Swiss–Webster counterparts (both tests), 129S2/SvHsd (but not 129/SvEv) mice exhibited evidence of higher anxiety, particularly in the LDE test. The implications of these findings are discussed in relation to both the behavioural and pharmacological phenotyping of mutant mice.