"This kind of mouse we raised under these conditions, and we changed nothing, but they varied in these ways over time"
I often wonder whether the variables we check against are actually as independent and subject to the central limit theorem as we assume.
Unsurprisingly, there's a ton of heterogeneity which means it's easy to violate your statistical assumptions (i.i.d. being more important than normality here, I think) and so you get a lot of false positives. It's similar to the brain imaging issue: the assumption of spatial locality and Gaussianness is not really true and drives a lot of false-positive _p_-value inflation. There are really quite a lot of problems with animal studies, so it's not a surprise that they wipe out spectacularly when transferring to human.
I keep a list of systematic reviews & meta-analyses I run across at https://www.gwern.net/DNB-FAQ#fn95 One of the most impressive ones, I think, are sepsis treatments: ~150 sepsis treatment experiments in humans based on mouse/rat experiments, and all of them failed: "Genomic responses in mouse models poorly mimic human inflammatory diseases", Seok et al 2013 http://www.pnas.org/content/110/9/3507.full.html
Also for the mice getting fatter over time? That's fascinating!
Well worth reading through the archives, IMO, even if you're not a chemist or biologist (I'm not). Quite aside from the methodological issues and the realities of working in the pharmacorp industry, Lowe's "Things I Won't Work With" series about dangerous chemical compounds is... a blast.
And of course there are similar issues with mice. You have all the different strains which are genetically different, but they'll also be genetically changing over time through drift & selection & mutations, so your Wistar-XXX may not be the Wistar-XXX from 50 years ago. Or mice chow - sure, the label may say it's the same but when was the last time you checked? (Think about that paper about how all sorts of lab animals, supposedly fed constant diets and under constant controlled environments, keep getting fatter over the past century. Something is changing; what? Genetics? Food composition? Micronutrients? Lab infections? Microbiomes? Measurement tools themselves?)