---------------------------------------- A World of Research On the Shoulders of a Mouse
By Abigail Trafford
Tuesday, July 29, 1997; Page Z06 The Washington Post
BAR HARBOR, Maine=97It turns out man's best friend is really the mouse.
Cute little quivering balls of fur, specially bred, clean and well-fed: black, white and sometimes brown, a Ralph Lauren tan that denotes the chic of genetic manipulation. More than 11,000 strains of mice are nurtured here at the Jackson Laboratory and sent to research centers all over the world, a catalogue of mice with gene names like stargazer and staggerer, ruby-eye and tippy, vibrator and velvet coat, angiotensin converting enzyme, neurotrophin-3 and twist.
Mickey and Minnie would be stunned by all the new members of the mouse family: inbred mice, hybrid mice, mice made to carry human genes, mice with a particular gene deleted -- the so-called knockout mouse -- so that scientists can see what that gene really does.
Without these research-friendly beasts, there would be far fewer discoveries of the genes involved with obesity or juvenile diabetes or epilepsy. Scientists who want to understand human genes can turn to mice to isolate a gene, manipulate it and monitor its impact over many generations.
To Leroy Hood, chairman of the department of molecular biotechnology at the University of Washington School of Medicine, the mouse is part of the Rosetta stone of genetics. Just as archaeologists were able to decipher Egyptian hieroglyphics by reading a version of the text in Greek and Demotic script (everyday Egyptian), scientists can unravel the human genetic blueprint, he says, by reading how genes are expressed in yeast and mice.
The mouse is also a living test tube for new drugs. Want to see if a drug may work against Lou Gehrig's disease? Try it in mice. The effect of a high-fat diet? Feed the rodent equivalent of a greasy double cheeseburger to mice specially bred for obesity. Looking for an animal model for Alzheimer's? Bingo, a mutated mouse that gets deposits in the brain similar to what doctors see in the autopsied brains of Alzheimer's patients. "Whether these mice will develop the larger behavior deficits is not clear," explains Donald Price of Johns Hopkins University School of Medicine. "In a few years we'll get a model that is identical to what we get in the elderly. I feel these are going to be very valuable."
So important is the mouse to experimental research that the Harvard Health Letter designated the 1990s as "The Decade of the Mouse."
Naturally, the scientists think they are in charge.
But sometimes the mice have the last word. Despite all the manipulation and careful monitoring by human researchers, a mouse will suddenly do its own thing and mutate. Nature is still random, even in the laboratory. An unexpected gene alteration will pop up in a mouse: Some morning there's a weird new mouse in the plastic bread-box-shaped container where these research mice spend their lives.
"I hear you got a mutant," says a colleague in the hallway to senior staff scientist Leslie P. Kozak, who runs one of Jackson's mouse fat farms.
The newest mutant is a flabby black female whose spine is twisted, her right paw limp and her hind legs paralyzed. She can barely move, using her left paw to haul herself around the wood shavings of her plastic home. She was bred to help scientists understand the link between the body's brown fat and obesity. But instead of being a model of obesity, this mutant mouse may well give up some genetic clues to spinal paralysis.
The next step is to isolate the paralysis-causing gene and see if anyone has found it before. If not, the mutant may go down in history as a bold discovery. This has happened before. Earlier this year, another mouse genetically manipulated for obesity started walking around like a drunk. This random tipsy mutant ended up in a recent report in the journal Nature as an important finding on the brain, explains Kozak. "These are surprises," he says. "This is serendipity."
Scientists need serendipity as they keep breeding and manipulating and watching and testing. And that means there's always full employment for a mouse in science.
For all their sacrifices, research mice have a pretty soft life. In fact, one of the biggest problems is keeping wild mice out of the laboratory. That's why there are black boxes every 30 feet around the research units -- mousetraps to capture stray invaders and keep them from getting inside where the temperature is controlled, there's plenty of food and medical science is moving steadily forward.
(US) A World of Research On the Shoulders of a Mouse
