There’s a big problem with treating laboratory mice, and it could affect study results

There’s a big problem with treating laboratory mice, and it could affect study results

Over 120 million laboratory rats and mice are used worldwide each year. Many are accustomed to examining debilitating conditions like cancer, arthritis, and chronic pain, and almost all spend their lives in small, empty, boxy cages: a kind of permanent lockdown.

Our new analysis shows that this restrictive artificial housing in rats and mice leads to chronic stress and alters their biology. This raises worrying questions about their well-being – and how well they represent typical human patients.

We identified these effects of housing by extracting data from over 200 studies examining the effects of cage design on health outcomes known to be stress-sensitive in humans, such as: B. Mortality rates and the severity of diseases such as cardiovascular disease, cancer and stroke.

The meaning of housing

The studies we synthesized compared traditional “shoeboxes”—the small, dreary cages typical of laboratories—to better-appointed housing with wheels, nesting boxes, extra space, or other items that enable natural behaviors such as digging, climbing, exploring, and hiding .

Overall, the animals in conventional cages got sicker than those in better equipped facilities. For example, when they got cancer, they developed larger tumors.

Conventionally kept animals were also at higher risk of dying, reducing their average lifespan by about 9 percent. Scientists have known for decades that rats and mice want more comfort, exercise, and stimulation than is normally provided, and that conventional cages therefore produce abnormal behavior and anxiety.

But this is the first evidence that they also cause chronic stresses severe enough to threaten animal health.

Mice in a cage with food materialWhen mice are kept in stimulating environments, they are healthier. (Aileen MacLellan/Author Provided)

Stressed Findings

Our study – like many others before us – also found evidence of methodological problems and poor reporting of experimental details. For example, the rodents used were male-biased, with few studies using female animals.

Furthermore, two-thirds of the studies in our analysis did not fully describe the living conditions of the animals, although the effects on housing were examined. Our results support many previous suggestions that rats and mice living in sterile cages without stimulation may not be suitable models for several reasons. Experimental animals are usually male, often overweight, sometimes with chronic colds and cognitive impairments.

We surmise that the reliance on “SHINE” animals—cold, plump, abnormal, male-biased, enclosed, and desperate—might explain the current low success rates of biomedical research. There are already examples of research studies that reach very different conclusions depending on how the animals are kept, and we want to assess to what extent this is the case.

That housing is critical to rodent biology but often poorly described in papers may also help explain the “replicability crisis”: that at least 50 percent of preclinical research results cannot be replicated when other scientists repeat a study.

Racks with housed miceHousing is critical to the welfare of laboratory mice. (Understanding Animal Research/Wikimedia Commons)

Canadian politics

Only 1 to 2 percent of all research animals in the world live in Canada, so why should Canadians care? Firstly, because it still causes 1.5 to 2 million animals to be unintentionally stressed: this worries everyone who cares for animals.

But if animal husbandry actually changes research results, then this also has a financial impact. Canada spends approximately $4 billion annually on health research.

According to US estimates, if half of that is based on animals, only 50 percent of which are reproducible, Canada can spend about CAD$1 billion a year on non-reproducible animal testing.

And even if studies are replicable, significantly less than 5 percent of them show a usable medical benefit for humans. This is in stark contrast to the Canadian public’s expectation that around 60 percent of animal testing results in new human medicines.

Canadian standards require mice to be provided with nesting materials that can keep them warm, but is it time to improve them further?

The “shoeboxes” that rats and mice currently live in should no longer be ignored as a neutral backdrop, but viewed as a determinant of health: one that we can modify, improve, and study. This would allow us to better model the various social determinants of human health while improving animal welfare. The conversation

Georgia Mason, Professor, Integrative Biology, University of Guelph and Jessica Cait, PhD Student, Integrative Biology, University of Guelph.

This article was republished by The Conversation under a Creative Commons license. Read the original article.

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