Circadian timekeeping in BALB/c and C57BL/6 inbred mouse strains.

Circadian rhythms of locomotion (wheel-running activity) in 12 inbred mouse strains were recorded for interstrain differences in tau DD, the endogenous (free-running) period of the circadian pacemaker measured in constant environmental darkness. The results indicate that 1 or more genetic loci influence the value of tau DD, and a large (50 min) difference in mean tau DD between 2 of the strains, BALB/cByJ and C57BL/6J, allowed further characterization of the origins and inheritance of the polymorphic expression of this circadian pacemaker property. The interstrain difference in mean tau DD was associated with an interstrain difference in light-induced shifts of the phase of the free-running locomotor rhythm; the BALB/c strain (with the shorter mean tau DD) displayed relatively fewer advance phase shifts. Neither the history of previous light exposure, albinism, nor elevated circulating testosterone levels could account for the interstrain difference in mean tau DD. The value of tau DD based on the circadian rhythm of drinking activity (with the running wheel removed) was longer than that based on locomotion; this discrepancy was significantly greater and more variable in BALB/c than in C57BL/6 mice, though the interstrain difference in mean tau DD could not be attributed entirely to this effect. Reciprocal F1 hybrids of BALB/c x C57BL/6 matings revealed dominance of the C57BL/6 genotype, no sex linkage, and a significant (but small) maternal effect. Examination of CXB recombinant inbred strains provided no support for the hypothesis of monogenic inheritance. Further study of inherited differences in the BALB/c and C57BL/6 strains may be a useful noninvasive experimental approach for investigation of the neurobiological substrates of circadian rhythmicity.