Delivering a knockout

Scientists have finally engineered a rat with a chosen gene removed

Now there’s a real knockout.

That’s not something you hear very often about a rat. But for some rats in Qi-Long Ying’s lab, it’s true.

For the first time, scientists have succeeded in genetically engineering a rat by specifically removing a single gene, Ying and his colleagues report online August 11 in Nature. The process is known to geneticists as “knocking out” a gene; in this case, the gene encodes a powerful anticancer protein known as p53.

Rats are the lab animal of choice for a wide variety of studies, but until now, scientists could not genetically manipulate the animals to remove or add certain genes the way researchers have done with mice. Genetically engineering animals such as rats and mice requires the ability to make stem cells that can give rise to an entire animal, including the “germ line,” which produces eggs and sperm. Ying’s team at the University of Southern California in Los Angeles and another group of researchers finally succeeded in making such stem cells in 2008 (SN Online: 12/24/2008). The team had several more technical hurdles to overcome before delivering the knockout, Ying says.

Rats lacking the gene p53, which are likely to be used to study cancer and its treatment, will be available to researchers through a resource center at the University of Missouri in Columbia, he says. His team is now trying to create rats with weakened immune systems by knocking out two genes that encode key immune system proteins. Knockout mice with similar defects have been important in many types of medical research.

But Ying doesn’t expect scientists will beat down his door to learn how to genetically engineer rats — not yet anyway. “After so many years of failure, I think people have lost hope of doing gene knockouts in rats,” he says. “So it will take awhile for people to realize that this technology is available.”

Tina Hesman Saey is the senior staff writer and reports on molecular biology. She has a Ph.D. in molecular genetics from Washington University in St. Louis and a master’s degree in science journalism from Boston University.

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