Comfy Mice Leads to Better Science Says Stanford Researcher

Posted on April 2, 2012

Nine out of 10 drugs successfully tested in mice and other animal models ultimately fail to work in people. Joseph Garner, PhD, associate professor of comparative medicine at Stanford University School of Medicine, believes one reason for the failure may be because laboratory mice are too cold. Garner, who conducted the a study on mice at Purdue University, with graduate student Brianna Gaskill, says lab mice are routinely housed in chilly conditions, which may affect their well-being as well as the outcome of research studies.

Garner says, "If you want to design a drug that will help a patient in the hospital, you cannot reasonably do that in animals that are cold-stressed and are compensating with an elevated metabolic rated. This will change all aspects of their physiology - such as how fast the liver breaks down a drug - which can't help but increase the chance that a drug will behave differently in mice and in humans."

Garner and his colleagues suggest providing mice with materials so they can build a nest. With nests the mice can naturally regulate their temperatures to what is comfortable for them.

Garner says, "Why not let them do what they do in the wild, which is build nests? Mice can happily infest a meat freezer, with temperatures far below zero, but they survive and breed because they build these wonderful nests."

Given the option, the researchers say mice gravitate to temperatures of between 30 and 32 degrees Celsius (about 86 and 90 degrees Fahrenheit). But based on federal regulations, U.S. research laboratories are routinely kept between 20 to 24 degrees C. These cold temperatures do help curb aggressive tendencies in mice. Female mice also lactate better in cooler temperatures, although their pups don't do as well in the cold. Garner also says the when kept at temperatures on the colder end of the scale (18 to 20 degrees C) the mice show immune function changes and their growth may be retarded. Garner says mice may be compromised physiologically at this temperatures, which could affect research results.

Garner and his colleagues studied 36 male and 36 female mice of common strains. They created sets of two cages linked by a small tube so the mice could travel back and forth between the cages. One cage in each set was maintained at 20 C (68 degrees F) and was equipped with varying quantities of shredded paper, which the animals could use to build nests and snuggle in. The other cage was kept at one of six temperatures: 20, 23, 26, 29, 32 or 35 degrees C (68, 73, 79, 84, 90 or 95 F), but without nesting material.

The researchers found that each strain and sex had slightly different preferences. None was content to simply sit out the cold. The mice would either move to a toastier location, if available, or build elaborate, dome-like nests to warm themselves. The more nest-building material they had, the more they were willing to settle for a cooler clime. Some of the mice would even spend hours collecting strands of paper from the cold cage and transporting it to a more comfortable spot in the warmer cage.

Garner said some mice wanted to have it all and would choose a warm spot and build a nest there as well. Garner says, "Naughty little rascals. They would go on holiday somewhere warm AND take their nest with them. Some people like to take a pillow on holiday and some don't. These mice were packing their own pillow."

Garner says the movement of paper for nests to the warmer cages means the nest may also serve a function beyond warmth, such as decreasing mice anxiety and stress levels. Garner says mice nests also makes it easier to see how the mice are faring.

He says, "The shape of the nest tells an experienced person whether the animals are too hot or too cold, whether they are sick or whether they are about to give birth. Once you learn how to 'speak mouse nest,' the nest is a wonderful tool that anyone can use to assess the general state of the mouse."

Garner has also argued that adding environmental variables to mouse testing would increase testing accuracy.

The research was published here in PLoS One.

MICE