01992nas a2200241   4500000000100000000000100001008004100002260001100043653001900054653001900073653002400092653001700116653002000133100002300153700002500176700001800201245017800219856004400397300000800441490000700449520128000456022001401736       2022                            d  c2022/110aanimal welfare10achronic stress10ahousing temperature10amouse models10areproducibility1 aBonnie L. Hylander1 aElizabeth A. Repasky1 aSandra Sexton00aUsing Mice to Model Human Disease: Understanding the Roles of Baseline Housing-Induced and Experimentally Imposed Stresses in Animal Welfare and Experimental Reproducibility  uhttps://www.mdpi.com/2076-2615/12/3/371  a3710 v123 aMice are the most common animal used to study disease, but there are real concerns about the reproducibility of many of these experiments. This review discusses how several different sources of chronic stress can directly impact experimental outcomes. Mandated housing conditions induce an underappreciated level of chronic stress but are not usually considered or reported as part of the experimental design. Since chronic stress plays a critical role in the development and progression of many somatic diseases including cancer, obesity, and auto-immune diseases, this baseline stress can directly affect outcomes of such experiments. To study the role of stress in both physical and psychiatric diseases, there has been a proliferation of protocols for imposing chronic stress on mice. For somatic diseases, biomarkers can be used to compare the models with the disease in patients, but to evaluate the validity of psychiatric models, behavioral tests are carried out to assess changes in behavior and these tests may themselves cause an underappreciated degree of additional stress. Therefore, it is important for animal welfare to reduce baseline stress and select the most humane protocols for inducing and assessing chronic stress to obtain the most reliable outcomes.  a2076-2615