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Sunday, May 6, 2012

Lab mice made comfy for relevant test results

One of the major complaints animal activists lodge against using other species to test drugs that are ultimately meant for humans is that few substances actually translate between monkeys and men or mice and men.

“Mice predict the effect (of a substance) on humans with about 43 percent efficiency,” said Dr. Thomas Hartung, director of the Center for Alternatives to Animal Testing at Johns Hopkins University.

Overall, nine of 10 drugs tested in mice and other animals wind up not working on people. Researchers such as Hartung look for new methods to screen chemicals for toxicity and medicines for human benefit that don’t involve animals.

While those efforts are making some progress, biomedical research in the United States continues to use up to 100 million lab animals a year – almost all of them rats and mice. Scientists say they can’t just run tests on genes or cell cultures – they have to see how things work in complete organisms.

Over the last few decades, gene splicing has allowed researchers to customize and standardize all sorts of traits in lab animals, particularly rodents, to make them better models for various diseases.

At the same time, there have been advances in allowing lab animals to be more normal and natural, which may lend more relevance to the results.

Called “enrichment,” the field generally addresses anything that people can do to make life more interesting, less sterile or less stressful for animals confined to a cage or pen.

When it comes to the well-being of mice, one of the most savvy scientists is Joseph Garner, an associate professor of comparative medicine at Stanford University who has studied nesting behavior in lab mice for nearly seven years.

One of the things he has learned is that mice want to control their environment as much as possible. In particular, lab mice are usually cold – labs are typically kept from 68-75 degrees, but mice are happiest in the mid- to upper 80s.

The solution found by Garner, Briana Gaskill, of Charles River Laboratories, and colleagues in a new study is to give the animals enough insulating nesting materials that they can cozy up and regulate their temperature.

“If you want to design a drug that will help a patient in a hospital, you cannot reasonably do that in animals that are cold-stressed and are compensating with elevated metabolic rates,” Garner said in a statement.

Burning through calories speeds up many physical processes, including how fast the liver breaks down a drug, which makes it even more likely that the drug will function differently between mice and humans, the researcher noted.

The experiment, reported recently in the online journal PLoS One, gave mice of three common strains the choice of two cages linked by a plastic tube. One cage was always 68 degrees, but equipped with shredded paper to build nests; the other cage was kept at one of six temperatures from 68-95, but with no nesting material.

Although there were some differences among the strains, the mice generally went for the warmest spot and a nest to go with it. Many rodents would spend hours moving paper to a cage that was already toasty, suggesting that a nest offers some comfort or privacy that decreases the animals’ anxiety and stress levels, Garner said.

Keeping stress levels down is important for lab animals because it can bump up so many vital signs, from body temperature to blood glucose and insulin levels. Often, experiments are designed to induce some level of stress in test animals to measure the effect on the brain or immune system. But researchers can trigger stress simply by picking up an animal, skewing the impact of the actual test.

Researchers in England pointed out in the journal Nature Methods in 2010 that the standard practice of grabbing mice by their tails produced the most distress, and showed it was preferable to either scoop them up in a gloved hand or allow them to walk into a small plastic tube for transport.

The University of Liverpool scientists received an additional grant from the Wellcome Trust to teach their mouse-handling tricks to other researchers.

Lee Bowman is health and science reporter for Scripps Howard News Service. He can be reached at bowmanl@shns.com.