Scientists return to rat as biomedical research tool.

2003 JUN 12 - (NewsRx.com & NewsRx.net) -- Ever a favorite of biologists because of its record as a model to understand ailments like diabetes and cancer, the lab rat lost its luster as a research tool during the past decade because it defied attempts to manipulate its genome in a prescribed way.

Now, using a novel combination of tried-and-true techniques, scientists have created the first "knockout" rats, specifically rats whose genomes have been stripped of genes that suppress breast cancer. The development, reported May 19, 2003 by a team of scientists from the University of Wisconsin-Madison in online editions of the journal Nature Biotechnology, promises to restore the rat to biomedical prominence.

"People have tried for more than 10 years to produce a knockout rat," said Michael N. Gould, a professor of oncology at UW-Madison's McArdle Laboratory for Cancer Research, in whose laboratory the work was conducted.

For 100 years, he explained, the rat was the model of choice for many biomedical scientists. But a decade ago, when knockout technology was first widely deployed in the mouse, the sturdy rat was dethroned. Researchers rushed to take advantage of the biomedical possibilities of an animal model whose genome could be manipulated at will, adding or subtracting genes to gain surprising insight into a host of diseases and potential treatments.

The rat, said Gould, had been "compromised by the lack of a full genetic toolbox. Over the last 10 years, the government and drug companies have invested a lot in bringing the rat up to speed. But one of the last major elusive tools for our toolbox was the ability to knock out genes."

The ability to add or subtract genes to an animal's genome lends powerful insight into the basic mechanisms of disease. New methods of disease prevention and treatment in humans, as well as a better basic understanding of development, physiology and pathology have resulted from the ability of scientists to manipulate genes in living animals.

Prior to the advent of the knockout mouse, the rat was "the model of choice for studies in physiology, pathobiology, toxicology and neurobiology," said Gould. "Anybody that gave up rats because there wasn't a ...