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Nat Rev Endocrinol. 2017 Aug;13(8):458-465. doi: 10.1038/nrendo.2017.48. Epub 2017 May 12.

Warming the mouse to model human diseases.

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Cardiovascular Research Institute, University of California, San Francisco, 555 Mission Bay Boulevard South, San Francisco, California 94158, USA.
Department of Physiology University of California, San Francisco.
Department of Medicine, University of California, San Francisco, 505 Parnassus Avenue, San Francisco, California 94143, USA.


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.

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