Abstract
ObjectiveTo improve understanding of mouse energy homeostasis and its applicability to humans, we quantitated the effects of housing density on mouse thermal physiology in both sexes. MethodsLittermate wild type and Brs3-null mice were single- or group- (three per cage) housed and studied by indirect calorimetry with continuous measurement of core body temperature, energy expenditure, physical activity, and food intake. ResultsAt 23 °C, below thermoneutrality, single-housed males had a lower body temperature and unchanged metabolic rate compared to group-housed controls. In contrast, single-housed females maintained a similar body temperature to group-housed controls by increasing their metabolic rate. With decreasing ambient temperature below 27 °C, only group-housed mice decreased their heat conductance, likely due to huddling, thus interfering with the energy expenditure vs ambient temperature relationship described by Scholander. In a hot environment (35 °C), the single-housed mice were less heat stressed. Upon fasting, single-housed mice had larger reductions in body temperature, with male mice having more torpor episodes of similar duration and female mice having a similar number of torpor episodes that lasted longer. Qualitatively, the effects of housing density on thermal physiology of Brs3-null mice generally mimicked the effects in controls. ConclusionsSingle housing is more sensitive than group housing for detecting thermal physiology phenotypes. Single housing increases heat loss and amplifies the effects of fasting or a cold environment. Male and female mice utilize different thermoregulatory strategies to respond to single housing.
Highlights
Mice are a widely used research model for human diseases, including obesity and diabetes
Characteristics of single and group housing We studied the effects of housing density by comparing three mice per cage (“group”) vs one mouse per cage (“single”) under various conditions, including a 24-h fast and cold (8 C) and hot (35 C) ambient temperatures (Ta) (Figure 1)
Because minute-to-minute variation in core body temperature (Tb) correlates with physical activity, these results indicate some synchronization of activity patterns among the mice in a group cage
Summary
Mice are a widely used research model for human diseases, including obesity and diabetes. Mice are genetically tractable and easy to study, and genes and metabolic pathways are very highly conserved between the species. In mice, the mass-specific metabolic rate is w7-fold higher and the surface area:volume ratio is w14-fold higher than in humans. Better understanding of mouse thermal physiology is needed to drive experimental design, guide interpretation of results, and generally improve applicability of mouse observations to humans. Recent efforts to make mice a better model have focused on housing temperature [3e6]. Another environmental factor that impacts thermal physiology is housing density: group vs single housing
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