Warming the mouse to model human diseases

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. This allows humans to maintain a constant core temperature with minimal energy expenditure, a trait that is conserved across all endotherms, including mammals and birds. Although this primordial drive leads us to seek thermal comfort, we house our experimental subjects, laboratory mice (Mus musculus), under thermal stress conditions. Here 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 tumor immunology, we point out that certain phenotypes observed under thermal stress conditions 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 allow for more predictive modeling of human diseases and therapies.

Proteome Imbalance of Mitochondrial Electron Transport Chain in Brown Adipocytes Leads to Metabolic Benefits

“…Housing temperature affects BAT thermogenic capacity in mice (Cannon and Nedergaard, 2011; Ganeshan and Chawla, 2017). We therefore performed experiments at both RT and thermoneutrality.…”

“…The contribution of BAT adaptive thermogenesis to total energy expenditure is dependent on ambient temperature (Abreu-Vieira et al, 2015; Cannon and Nedergaard, 2011; Ganeshan and Chawla, 2017; Maloney et al, 2014). At room temperature (RT), BAT-mediated adaptive thermogenesis is already active, and defective adaptive thermogenesis is often associated with reduced energy expenditure and development of obesity in many animal models.…”

Macrophage‐derived HMGB1 is dispensable for tissue fibrogenesis

“…In the recent years, several striking studies have demonstrated that for rodent models, as opposed to thermoneutral housing (30-32°C), room temperature housing (20-22°C) initiates and maintains a chronic cold stress that dramatically impairs physiology and immune response (eg, to inflammatory stimulus). [36][37][38] As a severe alteration of immune responses has pronounced consequences on fibrosis progression, 39,40 we hypothesized that thermoneutral housing, rather than room temperature housing performed so far, might be a more relevant context to evaluate the impact of macrophagederived HMGB1 deletion on fibrosis development. For this purpose, after 2 weeks of acclimation at 30°C, HMGB1 Flox and HMGB1 ΔMac mice were subjected to two fibrosis models: BDL-induced liver fibrosis and UUO-induced kidney fibrosis.…”

Comparative proteomic study of liver lipid droplets and mitochondria in mice housed at different temperatures

“…Ganeshan et al . commented that warming the laboratory mouse might allow for more predictive modelling of human diseases and therapies.…”

“…Furthermore, mice housed at a standard temperature fail to mimic a number of human diseases [11][12][13][14]. Ganeshan et al [9] commented that warming the laboratory mouse might allow for more predictive modelling of human diseases and therapies.…”