Nine out of 10 drugs successfully tested in mice and other animalmodels ultimately fail to work in people, and one reason may betraced back to a common fact of life for laboratory mice: they'recold, according to a researcher at the Stanford University Schoolof Medicine. Laboratory mice, which account for the vast majority of animalresearch subjects, are routinely housed in chilly conditions, whichmay affect their well-being as well as the outcome of researchstudies, said Joseph Garner, PhD, associate professor ofcomparative medicine. "If you want to design a drug that will help a patient in thehospital, you cannot reasonably do that in animals that arecold-stressed and are compensating with an elevated metabolicrate," Garner said. "This will change all aspects of theirphysiology - such as how fast the liver breaks down a drug - whichcan't help but increase the chance that a drug will behavedifferently in mice and in humans." In a new study, Garner and his colleagues report finding an easysolution to the problem: Simply provide the animals with the propermaterials, and they'll build a cozy nest that allows them tonaturally regulate their temperatures to a comfortable level. Thesethermally content mice would be more physiologically comparable tohumans and thus might serve as more meaningful research subjects,Garner said.
"Why not let them do what they do in the wild, which is buildnests? Mice can happily infest a meat freezer, with temperaturesfar below zero, but they survive and breed because they build thesewonderful nests," he said. The study, part of nearly seven years of work with mouse nestingbehavior, is the first to "ask" mice to rate the value of nestingmaterial in terms of temperature savings, which is an importantfirst step in setting standards for nesting material, said Garner,whose work has focused on the well-being of the mouse. He is thesenior author of the study, which will be published online in PLoS ONE. Mice, which Garner calls "one of the most fantastic animals onEarth," have evolved in the same environment as humans forthousands of years, making them remarkably adaptable, able to livevirtually anywhere.
For that reason, they make excellent researchsubjects, with hundreds of millions of them populating laboratoriesaround the world. Given the option, mice gravitate to temperatures of between 30 and32 degrees Celsius (the equivalent of about 86 and 90 degreesFahrenheit). But based on federal regulations, U.S. researchlaboratories are routinely kept on the cold side - between 20 to 24degrees C.
There can be advantages to these cold temperatures. Forinstance, mice have aggressive tendencies that are suppressed incooler climes. Female mice also lactate better in coolertemperatures, 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 micebegin to show changes in immune function and their growth may beretarded. "So we're housing them right at that threshold," Garnersaid.
"That means the mice may be compromised physiologically,potentially affecting research results." Simply raising the temperature in the lab isn't an option, notleast because the mice would then become unmanageably aggressive,he said. Rather, Garner and his colleagues looked to other optionsin their study, which involved 36 male and 36 female mice of threecommon strains. The researchers created sets of two cages linked bya small tube so the mice could move between them. One cage in eachset was maintained at a chilly 20 degrees C (68 degrees F) and wasequipped with varying quantities of shredded paper, which theanimals could use to construct nests for shelter and warmth.
Theother cage was kept at one of six temperatures: 20, 23, 26, 29, 32or 35 degrees C (68, 73, 79, 84, 90 or 95 F), but without nestingmaterial. The mice then had the choice of staying put and tolerating thecold, choosing a balmier cage, eating more to add fat and elevatemetabolic rate, or building a nest. Each strain and sex had slightly different preferences, theresearchers found. None was content to simply sit out the cold,either moving to a toastier location, if available, or buildingelaborate, dome-like nests to warm themselves. The morenest-building material they had, the more they were willing tosettle 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 oftenwould spend hours collecting strands of paper, bit by bit, from thechilliest cage and then transporting it to a more comfortable spotin another cage to build a sturdy little home. Garner said these mice decided they wanted to have it all, choosinga warm spot and building a nest as well. "Naughty little rascals"is how he described them. "They would go on holiday somewhere warmAND take their nest with them," he said. "Some people like to takea pillow on holiday and some don't.
These mice were packing theirown pillow." The fact that some mice moved nesting material to the warmer cagemeans that the nests serve a function beyond warmth, argued Garner,perhaps providing physical comfort, or a form of protection thatdecreases the animals' anxiety and stress levels. The nest-building mice tended to eat less, as they didn't need theextra calories to satisfy their higher metabolic demands, theresearchers found. In general, the females preferred warmertemperatures than the males - by about 5 degrees: they are smallerand have less fat to generate heat. The researchers concluded that the mice could manage with 6 gramsof nesting material but sometimes could use as much as 10 grams,suggesting the larger amount be supplied routinely in researchlabs. Another benefit of the nests is that they facilitate researchers'work with the mice - it's easier to pick them up as well as observethem.
"The shape of the nest tells an experienced person whetherthe animals are too hot or too cold, whether they are sick orwhether they are about to give birth," Garner said. "Once you learnhow to 'speak mouse nest,' the nest is a wonderful tool that anyonecan use to assess the general state of the mouse." Additional References Citations. I am an expert from Automobiles & Motorcycles, usually analyzes all kind of industries situation, such as big dog choppers , genisys scan tool.
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