Mutant mice aid hunt for cures

They’re being bred now by the millions, the mutants, created to carry the ghastliest of diseases for the benefit of the human race. Since researchers published the mouse’s entire genetic

makeup in map form three years ago, increasingly exotic rodents are being created with relative ease. There’s the Schwarzenegger mouse, which is injected with muscle-building genes, and the

marathon mouse, which never seems to tire. Researchers recently engineered some mice to be extremely addicted to nicotine, and others to be immune to scrapie, a close cousin to the

brain-wasting mad cow disease. And scientists are in hot pursuit of a Methuselah mouse, able to cheat death long after its natural brethren meet their maker. Millions of these and other

mutant mice are routinely created by injecting disease-causing genes or by “knocking out” genes in mouse embryos. Their decreasing cost and increasing availability are helping researchers in

pursuit of all manner of disease cures. Top researchers in the Parkinson’s disease field, for example, were more excited by the dopamine-free “knock-out” mouse that Duke University

researchers invented than the actual study they unveiled this month, which suggested that the club drug Ecstasy reversed Parkinson’s-like effects in these particular bioengineered mice.

Researchers first genetically engineered a mouse in 1980. But until recently, such creations were mostly scientific novelties. That changed drastically after President Clinton announced the

mapping of the human genome in 2000. That’s because mice and men are nearly identical genetically, each possessing just a few hundred different genes out of a possible 25,000 or so. Cancer

in mice is a lot like human cancer, for instance. Mice have become powerful, living research tools. The number of mutant research mice has grown so dramatically in recent years that

companies are now profiting by housing and breeding scientists’ creations. “Space is precious,” said Terrence Fisher of Charles River Laboratories in Wilmington, Mass., the nation’s largest

mutant mouse house. The publicly traded company breeds and cares for scientists’ creations and markets their inventions to other researchers, shipping an estimated 7 million mice worldwide

annually. “The novelty of being simply able to do this has worn off, and clearly these mice are tools that are accelerating research,” Fisher said. Many animal rights groups oppose all

animal experimentation as cruel, but lab scientists who work with bioengineered mice point out that the Food and Drug Administration requires that all drugs be tested on animals before

people. Nearly all the genetically engineered mice in circulation today have but one gene added, subtracted or altered. The problem with that model is that many diseases such as diabetes and

cancer are caused by multiple gene malfunctions. “Eventually, that’s where engineered mice are going,” said Mendell Rimer, a University of Texas neuroscientist who tends to about 500 mice

in his Austin lab. “That’s a more realistic disease model.” Rimer’s genetically engineered mice are among the most advanced and offer a glimpse of the breakthroughs to come. He spent 2 1/2

years engineering mice with muscles that lose connection to their nerve cells. He’s done this by splicing into mice a cancer gene that creates a protein that “disassembles” the connections.

But he’s also taken his work one step further than the usual cut-and-paste work. Rimer is able to turn on the mutant gene by feeding the genetically engineered mouse an antibiotic. He can

turn it off by stopping the antibiotic treatment. This way, he can observe the progression and regression of the mutation he made, giving him unparalleled insight into how nerves communicate

with muscle. “We can control the timing of the defect that we induce in these mice,” Rimer said. “This type of complexity is where genetic engineering is heading.” MORE TO READ