Earlier, the unsuitability of mice in inflammation models was shown in a paper that should have been noted by anyone in the field. Just last month, a paper in Science detailed the problems with many animal studies (mouse and otherwise), particularly the smaller ones, which can suffer from bad statistics and poor protocols.
Now we have this, from PNAS. The authors, from the Roswell Park Institute and the EPA, say that standard rodent facility conditions are actually causing unintended chronic physiological stress:
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, ac- tivating 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. . .Overall, our data raise the hypothesis that suppression of antitumor immunity is an outcome of cold stress-induced thermo- genesis. 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.
As mentioned in that last line, the problem seems to be with the adaptive immune system – this effect is driven by CD8+ T cells in almost every case, and sometimes by changes in CD4+ cells as well. Overall, housing mice at the recommended temperatures, which are on the cool side, seems to promote a general immunosuppression, which I think it’s safe to say is not a factor that many people are taking into account. The animals have similar core body temperatures, but the extra burden of maintaining that in the cooler rooms is tipping some sort of balance – keeping all those immune systems running is apparently energetically costly, and they get downregulated.
This study looked at several sorts of tumorigenesis, but only for solid tumors, so the effects on leukemia, etc., are still unknown. You’d have to think, though, that several other disease areas could be affected by this situation as well – for example, how much of the uselessness of mice in inflammation models is caused by these changes? I’m simultaneously glad to see these things being uncovered, while being worried about how long it’s taken to uncover them: what else are we missing?