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World’s First Knockout Rats
By Kate Dalke

Look out, mice. Scientists may have a new best friend in the laboratory—the rat. For the first time researchers have “knocked out” a gene in rats, a trick that scientists have used to create hundreds of strains of mutant mice for genetics research.

The world’s first knockout rat, which has its BRCA2 gene disrupted.

Despite ten years of scientists trying to create a knockout rat, the technique that has catapulted mice into genetic stardom had, until now, flopped in rats.

In a new study, researchers have used a novel combination of relatively simple techniques to create two knockout rats. They introduced random mutations into male rats, and then bred them with females to create thousands of pups, which were screened for specific gene mutations.

“This is the genomic tool that was missing for rats,” says Michael N. Gould, a cancer researcher at the University of Wisconsin-Madison who led the study.

Rats are the preferred models for studying physiology of disease, particularly heart disease, diabetes and hypertension.

The research was time-consuming. It took nine months to create two knockout male rats, and the scientists screened some two thousand pups for mutations in the rat breast cancer suppressor genes Brca1 and Brca2.

Women whose BRCA1 and BRCA2 genes are damaged have a higher risk of developing breast cancer. The effect of knocking out these genes in the rats is not yet known.

Gould and his colleagues are looking forward to the completion of the rat genome sequence, which they say will be invaluable for future knockout studies.

In November 2002, researchers at Baylor College of Medicine in Houston, Texas, and other members of the rat genome consortium announced they had assembled the rat genome.

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Zan, Y. et al. Production of knockout rats using ENU mutagenesis and yeast-based screening assay. Published online in Nature Biotechnology (May 18, 2003).

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