Review Article | Published:

Warming the mouse to model human diseases

Nature Reviews Endocrinology volume 13, pages 458465 (2017) | Download Citation

Abstract

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.

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

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Acknowledgements

The authors thank members of the Chawla laboratory for discussions, and A. Loh for comments on the manuscript. Work in the authors' laboratories was supported by the US National Institutes of Health (NIH; grants DK094641, DK101064 and P30DK098722 to A.C.), and K.G. was supported by a postdoctoral fellowship from the Hillblom Foundation.

Author information

Affiliations

  1. Cardiovascular Research Institute, University of California, San Francisco, 555 Mission Bay Boulevard South, San Francisco, California 94158, USA.

    • Kirthana Ganeshan
    •  & Ajay Chawla
  2. Department of Physiology University of California, San Francisco.

    • Ajay Chawla
  3. Department of Medicine, University of California, San Francisco, 505 Parnassus Avenue, San Francisco, California 94143, USA.

    • Ajay Chawla

Authors

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Contributions

K.G. and A.C. researched data for the article, contributed to discussion of the content, wrote the article and revised and/or edited the manuscript before submission.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Ajay Chawla.

Glossary

Endotherms

Organisms that use internally generated heat to maintain a constant core temperature despite changes in environmental temperature.

Core temperature

The temperature of deep body organs, which exhibits minimal fluctuation at different ambient temperatures.

Ectotherms

Organisms that primarily rely on external heat sources to regulate their core temperature, which changes with environmental temperature.

Homeothermy

The maintenance of a stable core temperature regardless of environmental conditions or temperature.

Ambient temperature

The temperature of the environment in which an animal lives.

Thermoneutral zone

The range of ambient temperatures at which sufficient heat is generated by basal metabolism to maintain core temperature within a specified range.

Thermal comfort zone

The range of ambient temperatures, and associated humidity and air movement, at which clothed humans express satisfaction with their thermal environment.

Basal metabolic rate

The energy expended by an animal during the post-absorptive rest state in its thermoneutral environment.

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DOI

https://doi.org/10.1038/nrendo.2017.48

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