Warming the mouse to model human diseases

• Published in: Nature reviews. Endocrinology Vol. 13; no. 8; pp. 458 - 465
• Main Authors: Ganeshan, Kirthana, Chawla, Ajay
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.08.2017; Nature Publishing Group
• Subjects: 631/443/319/1557; 692/163/2743/137; 692/163/2743/393; 692/308/1426; Animal experimentation; Animals; Biology; Body Temperature - physiology; Body temperature regulation; Cholesterol; Cold; Cold Temperature - adverse effects; Disease Models, Animal; Endocrinology; Energy expenditure; Energy Metabolism - physiology; Food; Heat; Homeostasis; Homeostasis - physiology; Housing; Housing, Animal - standards; Humans; Laboratories; Medical research; Medicine & Public Health; Metabolic Diseases - metabolism; Metabolic Diseases - physiopathology; Metabolic disorders; Metabolism; Methods; Mice; Phenotypes; Physiology; review-article; Temperature; Thermogenesis; Tumors
• ISSN: 1759-5029; 1759-5037; 1759-5037
• DOI: 10.1038/nrendo.2017.48

Key Points Mice and humans prefer to live within their thermal neutral or comfort zone at which they expend the least amount of energy to maintain their core temperature The normal housing temperature (ambient temperature of 20–22 °C) is within the thermal comfort zone of clothed humans but below the thermoneutral zone (ambient temperature of 30 °C) of mice Housing of mice below their thermoneutral zone results in the activation of thermogenesis to maintain their core temperature Mice that are housed at ambient temperatures of 20–22 °C expend twice as much energy as those at ambient temperatures of 30 °C, which results is substantial changes in their metabolic, cardiovascular and immune responses Housing of mice at thermoneutrality might enable more predictive modelling of human physiology, diseases and therapeutics This Review provides a framework for understanding how ambient temperature affects metabolic, immune and cardiovascular phenotypes in mice, as well as the importance of ambient temperature on modelling of human diseases in these small rodents. Ganeshan and Chawla suggest that warming the mouse might enable more predictive modelling of human diseases and therapies. Humans prefer to live within their thermal comfort or neutral zone, which they create by making shelters, wearing clothing and, more recently, by regulating their ambient temperature. These strategies enable humans to maintain a constant core temperature (a trait that is conserved across all endotherms, including mammals and birds) with minimal energy expenditure. Although this primordial drive leads us to seek thermal comfort, we house our experimental animals, laboratory mice ( Mus musculus ), under conditions of thermal stress. In this Review, we discuss how housing mice below their thermoneutral zone limits our ability to model and study human diseases. Using examples from cardiovascular physiology, metabolic disorders, infections and tumour immunology, we show that certain phenotypes observed under conditions of thermal stress disappear when mice are housed at thermoneutrality, whereas others emerge that are more consistent with human biology. Thus, we propose that warming the mouse might enable more predictive modelling of human diseases and therapies.