Abstract

The mouse is the most important mammalian model in life science research and the behavior of the mouse is a key read-out of experimental interventions and genetic manipulations. To serve this purpose a solid understanding of the mouse normal behavior is a prerequisite. Using 14–19 months of cumulative 24/7 home-cage activity recorded with a non-intrusive technique, evidence is here provided for a highly significant circannual oscillation in spontaneous activity (1–2 SD of the mean, on average 65% higher during peak of highs than lows; P = 7E−50) of male and female C57BL/6 mice held under constant conditions. The periodicity of this hitherto not recognized oscillation is in the range of 2–4 months (average estimate was 97 days across cohorts of cages). It off-sets responses to environmental stimuli and co-varies with the feeding behavior but does not significantly alter the preference for being active during the dark hours. The absence of coordination of this rhythmicity between cages with mice or seasons of the year suggest that the oscillation of physical activity is generated by a free-running intrinsic oscillator devoid of external timer. Due to the magnitude of this rhythmic variation it may be a serious confounder in experiments on mice if left unrecognized.

Highlights

  • The mouse is the most important mammalian model in life science research and the behavior of the mouse is a key read-out of experimental interventions and genetic manipulations

  • Strains originating from the house mouse are currently the prevailing mammalian models in life science research

  • The free-running circadian rhythm (21–27 h) is generated endogenously by feedback loops involving key clock genes expressed by neurons in the Suprachiasmatic nucleus (SCN) of the hypothalamus that synchronizes with the earth’s solar day (24 h)

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Summary

Introduction

The mouse is the most important mammalian model in life science research and the behavior of the mouse is a key read-out of experimental interventions and genetic manipulations. Using 14–19 months of cumulative 24/7 home-cage activity recorded with a non-intrusive technique, evidence is here provided for a highly significant circannual oscillation in spontaneous activity (1–2 SD of the mean, on average 65% higher during peak of highs than lows; P = 7E−50) of male and female C57BL/6 mice held under constant conditions. This notion is building on the successful migration of the house mouse to almost every corner of the world attributed to the mouse capacity to adapt and reproduce in different environments across ­seasons[30,31] In line with this both the standardized care and use of laboratory mice commonly consider strain, age (seasons of the life-span), sex and the circadian rhythm as significant parameters but not seasonal (circannual) v­ ariations[30,32].

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