David, J. M., Stout, D. 2013. Individually ventilated cages impose cold-stress on laboratory mice: A source of systemic experimental variability. American Association for Laboratory Animal Science [AALAS] Meeting Official Program, 610 (Abstract #PS10).

Individual ventilated cages (IVC) have recently been increasing in popularity. Based on the high rates of ventilation with IVCs, we developed 3 hypotheses: first, mice housed in IVCs experience significantly more cold-stress than mice housed in static cages; second, the additional cold-stress imposed by IVCs will affect the results of experiments using mice to model human disease, and third, if provided shelters, mice will behaviorally thermoregulate and thereby rescue the cold-stress effects of IVCs. To test the hypotheses, we housed mice in 3 different housing systems: an IVC, an IVC with a shelter, or a static cage. We quantified cold-stress of each housing system on mice with 2 previously established metrics: nonshivering thermogenesis with thermography and brown adipose vacuolation with histology. To test housing effects in a common, cold-sensitive murine model of human disease, we implanted the mice with subcutaneous epidermoid carcinoma (A431) cells and quantified tumor growth, tumor metabolism, and adrenal weights of mice housed in each system. Mice housed in IVCs had significantly higher nonshivering thermogenesis, exhibited signs of cold-stress on histology, had smaller subcutaneous tumors, lower tumor metabolism, and larger adrenal weights compared with mice housing in static cages. Shelters rescued IVC-induced nonshivering thermogenesis and adrenal enlargement and partially rescued the histologic morphology of brown adipose tissue, and tumor size. IVCs impose chronic cold-stress on mice, alter experimental results, and act as a source of systemic confounder throughout rodent-dependent research. By allowing behavioral thermoregulation to occur via seeking shelter, we can partially rescue the experimental altering effects of housing imposed cold-stress, improve physiologic uniformity across housing systems, and increase experimental reproducibility across housing systems.