Laboratory mice, who account for the vast majority of animal research
subjects, are routinely housed in chilly conditions, which may affect their
well-being as well as the outcome of research studies, said Joseph Garner, PhD,
associate professor of comparative medicine.
"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 rate," Garner said. "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."
In a new study, Garner and his colleagues report finding an easy solution to
the problem: Simply provide the animals with the proper materials, and they'll
build a cozy nest that allows them to naturally regulate their temperatures to a
comfortable level. These thermally content mice would be more physiologically
comparable to humans and thus might serve as more meaningful research subjects,
Garner said.
"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," he said.
The study, part of nearly seven years of work with mouse nesting behavior, is
the first to "ask" mice to rate the value of nesting material in terms of
temperature savings, which is an important first step in setting standards for
nesting material, said Garner, whose work has focused on the well-being of the
mouse. He is the senior author of the study, which was published online March 30
in
PLoS ONE.
Mice, which Garner calls "one of the most fantastic animals on Earth," have
evolved in the same environment as humans for thousands of years, making them
remarkably adaptable, able to live virtually anywhere. For that reason, they
make excellent research subjects, with hundreds of millions of them populating
laboratories around the world.
Given the option, mice gravitate to temperatures of between 30 and 32 degrees
Celsius (the equivalent of about 86 and 90 degrees Fahrenheit). But based on
federal regulations, U.S. research laboratories are routinely kept on the cold
side -- between 20 to 24 degrees C. There can be advantages to these cold
temperatures. For instance, mice have aggressive tendencies that are suppressed
in cooler climes. Female mice also lactate better in cooler temperatures, though
their pups don't do as well in the cold.
When kept in temperatures toward the low end of this scale -- between about
18 and 20 degrees C (64-68 degrees F) -- the mice begin to show changes in
immune function and their growth may be retarded. "So we're housing them right
at that threshold," Garner said. "That means the mice may be compromised
physiologically, potentially affecting research results."
Simply raising the temperature in the lab isn't an option, not least because
the mice would then become unmanageably aggressive, he said. Rather, Garner and
his colleagues looked to other options in their study, which involved 36 male
and 36 female mice of three common strains. The researchers created sets of two
cages linked by a small tube so the mice could move between them. One cage in
each set was maintained at a chilly 20 degrees C (68 degrees F) and was equipped
with varying quantities of shredded paper, which the animals could use to
construct nests for shelter and warmth. 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 mice then had the choice of staying put and tolerating the cold, choosing
a balmier cage, eating more to add fat and elevate metabolic rate, or building a
nest.
Each strain and sex had slightly different preferences, the researchers
found. None was content to simply sit out the cold, either moving to a toastier
location, if available, or building 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, as the nests served to temper the chill, the
researchers found.
In fact, the nest-building drive was so strong that the mice often would
spend hours collecting strands of paper, bit by bit, from the chilliest cage and
then transporting it to a more comfortable spot in another cage to build a
sturdy little home.
Garner said these mice decided they wanted to have it all, choosing a warm
spot and building a nest as well. "Naughty little rascals" is how he described
them. "They would go on holiday somewhere warm AND take their nest with them,"
he said. "Some people like to take a pillow on holiday and some don't. These
mice were packing their own pillow."
The fact that some mice moved nesting material to the warmer cage means that
the nests serve a function beyond warmth, argued Garner, perhaps providing
physical comfort, or a form of protection that decreases the animals' anxiety
and stress levels.
The nest-building mice tended to eat less, as they didn't need the extra
calories to satisfy their higher metabolic demands, the researchers found. In
general, the females preferred warmer temperatures than the males -- by about 5
degrees: they are smaller and have less fat to generate heat.
The researchers concluded that the mice could manage with 6 grams of nesting
material but sometimes could use as much as 10 grams, suggesting the larger
amount be supplied routinely in research labs.
Another benefit of the nests is that they facilitate researchers' work with
the mice -- it's easier to pick them up as well as observe them. "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," Garner
said. "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."
**Published in "SCIENCE DAILY"
