Thermal physiology of laboratory mice: Defining thermoneutrality

Gordon, Christopher J.

doi:10.1016/j.jtherbio.2012.08.004

Cited by 243 publications

(299 citation statements)

References 89 publications

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“…Physiologists have found major differences between the thermal physiology of mice, other mammals, and humans [3,[5][6][7][8][9][10][11][12], such that at ambient temperatures in which humans feel comfortable, mice experience chronic mild cold stress directly impacting their metabolism and thermoregulatory status. Laboratory mice are almost always housed and studied at mildly cool temperatures well below their 'thermoneutral zone' which is the ambient temperature in which metabolic heat production is minimal and the mouse does not need to work to keep warm or cold.…”

Section: Room Temperature: So Much More Than a Thermometer Readingmentioning

confidence: 99%

“…Laboratory mice are almost always housed and studied at mildly cool temperatures well below their 'thermoneutral zone' which is the ambient temperature in which metabolic heat production is minimal and the mouse does not need to work to keep warm or cold. It is the ambient temperature at which a stable core temperature can be maintained by the basal metabolism of the animal at rest and by 'adjustments in insulation, posture, and skin blood flow' [6]. For healthy mice, this thermoneutral temperature (TT, see Glossary) is generally 30-32 8C, and it has been known for many decades that, given a choice, mice will choose to spend the majority of time in this range [13].…”

Section: Room Temperature: So Much More Than a Thermometer Readingmentioning

confidence: 99%

Section: Glossarymentioning

confidence: 99%

“…This dichotomy between the mandated, standard temperature (sub-thermoneutral temperature, ST) and the thermoneutral temperature (TT) is acknowledged in the Guide, which recommends that mice be provided with nesting materials or shelter (see also [25,26]). However, these measures are not always in place, and even when they are, mice are often seen to 'huddle' to minimize heat loss and exhibit signs of cold stress [6]. Researchers have noted a variety of significant differences in mice housed at ST versus TT, including differences in basal metabolism [12], cardiovascular physiology [27,28], the size of organs and tail length [29], and the effects of hypoxia on lipolysis during thermogenesis [30].…”

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Thermoneutrality, Mice, and Cancer: A Heated Opinion

Hylander

Repasky

2016

Trends in Cancer

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Section: Room Temperature: So Much More Than a Thermometer Readingmentioning

confidence: 99%

Section: Room Temperature: So Much More Than a Thermometer Readingmentioning

confidence: 99%

Section: Glossarymentioning

confidence: 99%

mentioning

confidence: 99%

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Thermoneutrality, Mice, and Cancer: A Heated Opinion

Hylander

Repasky

2016

Trends in Cancer

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“…This factor is important because mice have a high surface area to body mass ratio and lose heat rapidly. In nature, mice seek warm environments and build nests to minimize metabolic demands for heat production (3), and thermal preference studies have clearly shown that healthy mice will select an ambient temperature of 30-31°C (termed "thermoneutrality") at which their basal metabolism is sufficient to maintain body temperature (3)(4)(5)(6)(7). However, at subthermoneutral temperatures, mice experience cold stress, which induces a systemic sympathetic response involving adaptive metabolic changes and secretion of catecholamines, particularly norepinephrine (8).…”

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Baseline tumor growth and immune control in laboratory mice are significantly influenced by subthermoneutral housing temperature

Kokolus¹,

Capitano²,

Lee³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

266

288

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We show here that fundamental aspects of antitumor immunity in mice are significantly influenced by ambient housing temperature. Standard housing temperature for laboratory mice in research facilities is mandated to be between 20-26°C; however, these subthermoneutral temperatures cause mild chronic cold stress, activating thermogenesis to maintain normal body temperature. When stress is alleviated by housing at thermoneutral ambient temperature (30-31°C), we observe a striking reduction in tumor formation, growth rate and metastasis. This improved control of tumor growth is dependent upon the adaptive immune system. We observe significantly increased numbers of antigen-specific CD8 + T lymphocytes and CD8 + T cells with an activated phenotype in the tumor microenvironment at thermoneutrality. At the same time there is a significant reduction in numbers of immunosuppressive MDSCs and regulatory T lymphocytes. Notably, in temperature preference studies, tumor-bearing mice select a higher ambient temperature than non-tumor-bearing mice, suggesting that tumor-bearing mice experience a greater degree of coldstress. Overall, our data raise the hypothesis that suppression of antitumor immunity is an outcome of cold stress-induced thermogenesis. Therefore, the common approach of studying immunity against tumors in mice housed only at standard room temperature may be limiting our understanding of the full potential of the antitumor immune response. murine tumor models | metabolism

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Of mice and men – environmental temperature, body temperature, and treatment of obesity

Reitman

2018

FEBS Letters

103

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Mice are widely used for exploring obesity physiology and treatment. However, thermal biology is different between small and large mammals. In this Review, we discuss how the effect of environmental temperature must be understood to ensure applicability of mouse experiments to human obesity. At ambient environmental temperature (~ 22 °C), over one-third of energy expenditure in mice is devoted to maintaining core body temperature, largely by brown adipose tissue. To conserve this energy, mice can enter a regulated hypothermia, while humans do not. Since humans expend little or no energy specifically to keep warm, mice studied at thermoneutrality (~ 30 °C) may be a better model for human energy homeostasis. Studies indicate that environmental temperature also affects the efficacy of drugs that increase energy expenditure. In mice, dinitrophenol, a protonophore, and CL316243, a β3-adrenergic agonist, both increase metabolic rate at thermoneutrality, but only CL316243 increases it at 22 °C. Furthermore, mice housed at thermoneutrality may become more obese than mice at 22 °C. Thus, we discuss the importance of studying mice at both thermoneutrality and at lower temperatures in obesity research.

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Thermal physiology of laboratory mice: Defining thermoneutrality

Cited by 243 publications

References 89 publications

Thermoneutrality, Mice, and Cancer: A Heated Opinion

Thermoneutrality, Mice, and Cancer: A Heated Opinion

Baseline tumor growth and immune control in laboratory mice are significantly influenced by subthermoneutral housing temperature

Of mice and men – environmental temperature, body temperature, and treatment of obesity

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