Knockout Rats

Missing something? One of the world's first knockout rats.

Long considered the critter of choice for many genetic experiments, the mouse may now get some competition from its previously spurned cousin, the rat. A report in the 18 May issue of Nature Biotechnology reveals that, for the first time, researchers have successfully turned off a gene in rats.

Rats are preferred over mice when it comes to studying diseases like breast cancer and heart disease because their physiology is similar to that of humans. Unfortunately, scientists haven't been able to add or remove genes from rat DNA, so they've made do with mice. "A lot of people just think the mouse is a little rat," says Michael Gould, a geneticist and oncologist at the University of Wisconsin, Madison, and lead author on the paper. Actually, he says, rats and mice resemble each other about as much as humans and ferrets do.

To further their studies with the breast cancer genes BRCA1 and BRCA2, Gould and colleagues set out to create rats missing these genes. Mutant mice are traditionally crafted by disabling genes in embryonic stem cells, but no one could get rat stem cells with incapacitated genes to survive in the laboratory. So the researchers used a different approach: They injected male rats with a chemical called ENU that randomly scrambles single DNA bases. The genetically modified males were then bred with normal females to produce large litters. Among the thousands of offspring, the team found a handful of rats with mutations in BRCA1 and BRCA2.

Although the technique is less direct than the one used to create knockout mice, Gould says it is a cheap and easy way to find mutants and probably the best method to use until researchers figure out how to keep rat embryonic cells alive. "We've rejuvenated the rat as a biomedical model," he says. Others agree. "I think that this is a tremendous success," says Howard Jacob, a pharmacist and quantitative geneticist at the Medical College of Wisconsin in Milwaukee.

Related sites
Rat Genome Project at Baylor School of Medicine
Michael Gould's site

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