Mice Do Not Habituate to Metabolism Cage Housing–A Three Week Study of Male BALB/c Mice

Abstract

The metabolism cage is a barren, non-enriched, environment, combining a number of recognized environmental stressors. We investigated the ability of male BALB/c mice to acclimatize to this form of housing. For three weeks markers of acute and oxidative stress, as well as clinical signs of abnormality were monitored. Forced swim tests were conducted to determine whether the animals experienced behavioral despair and the serotonergic integrity was tested using an 8-OH-DPAT challenge. The metabolism cage housed mice excreted approximately tenfold higher amounts of corticosterone metabolites in feces throughout the study when compared to controls. Urinary biomarkers confirmed that these mice suffered from elevated levels of oxidative stress, and increased creatinine excretions indicated increased muscle catabolism. Changes in the core body temperature (stress-induced hyperthermia) and the fur state of the mice also indicated impaired well-being in the metabolism cage housed mice. However, monitoring body weight and feed intake was found misleading in assessing the wellbeing of mice over a longer time course, and the forced swim test was found poorly suited for studying chronic stress in mice in the present setup. In conclusion, the mice were found not to acclimatize to the metabolism cages whereby concern for animal welfare would dictate that mice should be housed in this way for as short periods as possible. The elevated degree of HPA axis activity, oxidative stress, and increased overall metabolism warrant caution when interpreting data obtained from metabolism cage housed mice, as their condition cannot be considered representative of a normal physiology.

Repeated dose (28-day) administration of silver nanoparticles of varied size and coating does not significantly alter the indigenous murine gut microbiome

“…Alterations in the cultivable fraction will thus have to be assessed in terms of their functional significance to the whole gut microbial community. Multiple factors, ranging from diet to intestinal microbiota, can affect gut microbial composition and stochastic effects can generate significant inter-individual variation, even in genetically identical animals and even with identical starting microbial populations (Kalliokoski et al, 2013). Thus AgNP-associated alterations, such as a decrease in cultivable bacteria will have to be assessed in light of inter-animal variation and functional significance to host health, before concluding that this alteration represents an adverse effect.…”

“…Since the majority of intestinal microbes cannot be cultured using standard microbiological techniques, culture-independent methods of microbial profiling, such as next generation sequencing and metagenomics, have been employed to further our understanding of intestinal microbial communities and the effects of their perturbation on human and animal health (Zoetendal et al, 2004). Alterations in gut microbiota have been associated with many gastro-intestinal and extra-digestive diseases (reviewed in (Kalliokoski et al, 2013, Morones-Ramirez et al, 2013). Additionally, a vast array of different substances may alter the gut microbiome.…”

Sodium homeostasis is preserved in a global 11β‐hydroxysteroid dehydrogenase type 1 knockout mouse model

“…However, mice housed in metabolic cages have been reported to display hypothalamic–pituitary–adrenal axis activation (manifesting as elevated faecal excretion of corticosterone) that is sustained for up to 3 weeks (Kalliokoski et al . ). Such an effect may have masked subtle differences in corticosterone excretion and renal fluid–electrolyte metabolism between the Hsd11b1 −/− and control groups.…”

“…We included a 5 day acclimation period, which should provide sufficient time for the stabilization of urine output and urinary electrolyte excretion (Stechman et al 2010). However, mice housed in metabolic cages have been reported to display hypothalamic-pituitary-adrenal axis activation (manifesting as elevated faecal excretion of corticosterone) that is sustained for up to 3 weeks (Kalliokoski et al 2013). Such an effect may have masked subtle differences Figure 7.…”

Mouse Behavior Tracker: An Economical Method for Tracking Behavior in Home Cages

“…For some strains, altered behavior has been observed even after 3 weeks of habituation to a commercial metabolic cage system (11). Some commercial systems can analyze behavior in home cages, but one such system does not measure distance traveled (HomeCageScan; CleverSys Inc, Reston, VA), and another system monitors activity but does not accurately measure distance traveled (Infrared Motion Detector; Starr Life Sciences Corp., Oakmont, PA).…”