Not the right way to handle mice? Credit: Patrice Latron/Corbis

Picking up mice at the base of the tail is standard practice in laboratory research, but whether this is the best method is unclear. Researchers now suggest that cupping a mouse in the hand or carrying it in a small tunnel reduces stress and encourages cooperation.

As prospective prey for many animals, mice are understandably nervous when someone seizes their tail. Yet scientists do this regularly, in part to avoid being bitten. Gripping mice in this way increases their anxiety and decreases the likelihood that they will voluntarily interact with experimenters, according to a study led by Jane Hurst, a behavioural biologist at the University of Liverpool, UK, published online in Nature Methods1 today.

The researchers placed male and female mice from three strains into one of three experimental groups. Some mice were lifted by the base of the tail and held on a gloved hand or lab-coat sleeve. A second group of mice crawled into an acrylic tunnel filled with a familiar scent. In the third group, the handlers scooped mice up with gloved hands that loosely closed around the animals until the mice had adapted to the routine. Each of the 9-16 daily sessions lasted 1 minute.

Carrying mice in tunnels or cupping them in the hand may help to keep them calm. Credit: Jane Hurst

Cupping or carrying the mice in tunnels increased their interactive behaviour with the handlers compared with hoisting them by the tail. When the experimenters held a tunnel or hand in the front half of the cage for 1 minute, mice that were accustomed to these procedures spent more time sniffing, chewing and climbing on top of the tunnel or hand compared with those that had been grabbed by the tail. And the mice entered an open, unprotected arm of a maze more frequently — a sign of reduced anxiety.

By contrast, tail-grasping caused the mice to urinate and defecate more — behaviours that often signal distress. Less-anxious mice did not avoid handlers that restrained them by the scruff of the neck, whereas tail-snatched mice scurried away.

Troubling tail

The findings confirm what many stress researchers already know, says Darlene Francis, a behavioural neuroscientist at the University of California, Berkeley. Researchers in her lab always cup mice because they want to avoid extraneous variables that could alter measures of stress. Still, she says, it is important to systematically assess the effects of different handling practices on behaviour. "The animals habituated to the tunnel and cupping methods pretty quickly," she says. "The authors have convincingly demonstrated that the techniques are fairly straightforward and simple."

"The paper has made me rethink some of the things we do," says Scott Russo, a behavioural neuroscientist at Mount Sinai Medical Center in New York. His lab members routinely clutch mice by the tail, even though they investigate the effect of stress on anxiety, depression and addiction. "Tail handling could absolutely influence the effects we observe," he says. Anxiety behaviour in mice is notoriously inconsistent — it fluctuates across strains, and even across days, he says. "If this is a way to reduce inter-experimental variability, this would be a very important finding."

In addition to improving the robustness of results across a range of research topics — from cancer to the immune system — the alternative procedures may represent a key refinement in the treatment of animals, says Hurst. In the future, she will work with various scientists at her institution to measure the influence of handling practices on physiological responses and the reliability of experimental results.

But switching methods mid-stream could complicate comparisons between old and new studies, says Des Smith, a behavioral geneticist at the University of California, Los Angeles. "If one tried to analyse all possible variants of all possible practices at every stage of every behavioural test, we could end up in a black hole and not actually move forward with the science." But, he adds, "This study has raised an interesting and provocative issue that might fuel the fires of discussion for some time to come."