Nine out of 10 drugs successfully tested in mice and other animal models ultimately fail to work in people, and one reason may be traced back to a common fact of life for laboratory mice: they're cold, according to a researcher at the Stanford University School of Medicine. Laboratory mice, who account for the vast majority of animal research subjects, are routinely housed in chilly1 conditions, which may affect their well-being2 as well as the outcome of research studies, said Joseph Garner3, 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 compensating4 with an elevated metabolic5(代谢的) rate," Garner said. "This will change all aspects of their physiology6 -- 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 cozy7(舒适的) nest that allows them to naturally regulate their temperatures to a comfortable level. These thermally8 content mice would be more physiologically9 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 infest10 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 savings11, 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 remarkably12 adaptable13, 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(趋向) temperatures of between 30 and 32 degrees Celsius14 (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 retarded15. "So we're housing them right at that threshold," Garner said. "That means the mice may be compromised physiologically, potentially affecting research results."