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It's a cozy rat's life at UM lab

Making them at ease aids research 
Ann Arbor News
Tuesday, December 27, 2005 

It's hard to believe Janet Hoff was once a little nervous handling rats. The mice she could deal with just fine. Rats were another matter. Today, she has no such reservations. On a recent tour of her lab at the University of Michigan, Hoff twice asked a visitor if he wanted to see the rats. No, not really, we'll stick with the mice, came the reply.

But Hoff wasn't about to be dissuaded. She reached into a cage and picked up one of the rats, and then cradled it like a house pet in the crook of her arm. She scratched it gently behind the ear. "Rats like to be scratched behind the ear,'' Hoff explained. In that way, they're just like dogs, she said.

Working with these rats and mice, U-M researchers are seeking to gain a better understanding of the biology of diseases like hypertension and diabetes. It is hoped that the research will eventually lead to treatments for those diseases in humans.
Now here's where Hoff enters the equation.

To measure the animals' metabolic functions, researchers have to get them to perform exercises that might sound simple, but require patience and a certain touch. The mice and rats have to be made to walk in a straight line to judge their gaits, shimmy across a balance beam to examine their movements, and sit still so an instrument can record their blood pressures. All the while, they have to be comfortable, or the results will be skewered because of the effect that stress has on the animals' metabolic functions.

And for their part, the researchers can't be squeamish about handling the animals.

Hoff, a research associate and coordinator of U-M's Center for Integrative Genomics, teaches the researchers how to get their animals to perform. In some cases, she does the work herself.

"Confidence is a huge thing,'' Hoff said. "If you're comfortable and confident the animal will be.''

A nervous, jumpy researcher will put the animals ill at ease, and the test results won't be accurate.

"Animals are much more in tune with their environment,'' Hoff said. "Like Spiderman's spider sense, they sense things. Because that's their way of life. This sense of danger. They get ready, and when they need to, they run.''

Before he met Hoff, Dr. Mike Shillingford had no experience with laboratory animals. The general surgery resident at U-M is using mice that are bred without a certain gene and bought for study by the university.

The mice develop a condition similar to muscular dystrophy in humans. Shillingford wants to understand how the disease affects the heart, among other things. While they're not in pain, the mice are so fragile that they might die if put under a great amount of stress.
Hoff was his "lifeline,'' Shillingford said. "Without her, it wouldn't be possible.''

Hoff always loved working with animals. Prior to coming to U-M in 1996, Hoff managed a thoroughbred race horse farm and worked as a licensed veterinary technician. In 2002, she was named as coordinator of the U-M center

Earlier this year, she rekindled her love of horses, opening the Equine Charm School in the Waterloo area. She has three horses, and boards three more. She gives riding lessons, and plans to start working with horse owners and their horses, to teach them how to train their animals.

When she began working with laboratory animals, Hoff said, it wasn't much of a stretch to apply what she learned about animals' behaviors from working with horses, dogs and cats.

Before you feel badly for the animals, most do not have surgery performed on them, though in some cases researchers transplant genes in the animals to study their affect on disease progression. The experiments are strictly regulated, Hoff said. The mice and rats get fresh food and water regularly, and have their bedding changed frequently, too. Once a disease has progressed to cause the animal to suffer, the animal is euthanized.

After Hoff came to U-M, she modified or designed some of the tests to make the animals less stressed-out.

"I like working with animals and people,'' Hoff said. "And I get to invent things.''

Hoff took a mouse out of its cage to demonstrate a test that examines its physiology using a balance beam held in place in a clear plastic box. The bottom is padded so a mouse won't be hurt if it falls. A researcher would watch the mouse shimmy along the balance beam, looking for hesitations and slips of its feet. Speaking in a calm soothing voice to the mouse, Hoff placed the mouse on the balance beam and then applied her strategy for getting it to begin the exercise. She gently irritated its fur, pausing when the mouse began to move. When it stopped, she bothered it again.

"A nudge doesn't work,'' she said. "When you push against an animal, the animal wants to push back.''

On its first attempt, the mouse showed its agility and scampered across the balance beam without much of a problem until it reached the other side, where Hoff let it rest for awhile. As a reward, she didn't give it food or water. In fact, she didn't give it anything.

"That's their ultimate reward,'' she said. "to be left alone.''

Reporter: Dave Gershman