Posted on behalf of Ewen Callaway

The lab rat could be in for a comeback.

Over the last two decades, geneticists have increasingly turned away from rats and to mice because of the ease with which mouse genes can be removed, inserted or otherwise modified. This approach, called gene targeting, snagged a Nobel in 2007.

Now, researchers publishing in Nature have used the same technique to create rats missing a specific gene, in this case p53 – a tumour-suppressor known as ‘the guardian of the genome’.

“The mouse has really taken off and the rat has lagged a little, but now that we have these genetic engineering techniques for the rat, I really do think it’s going to be transformational,” says John Critser, director of the Rat Resource and Research Center at the University of Missouri in Columbia, who was not involved in the new study.

Timothy Aitman, at Imperial College London, calls the paper “a major breakthrough” that should help speed the return of the rat to genetics labs.

The new approach, developed by Qi-Long Ying’s team at the University of Southern California in Los Angeles, is not the first to create a transgenic rat, or even a knockout (KO) rat missing a gene.

Last year, a team at the University of Wisconsin used a DNA-clipping enzyme called a zinc finger nuclease to inactivate specific genes. But this approach is haphazard, says Ying, because it does not let scientists swap in and out specific DNA sequences, as gene targeting does.

But gene targeting also requires a healthy stock of embryonic stem cells, which had been unobtainable in rats until Ying’s team and another found a way to keep them from turning into other cell types using a cocktail different from the one traditionally used to maintain mice ES cells. From there, Ying followed the same procedures that researchers all over the world use to create knockout mice. He says the efficiency with rats is similar.

So far, the knockout rats are a proof of principle. Ying’s team chose p53 because it is among the most studied in the biology. His team has just begun studying the rodents and they plan to determine how missing p53 affects their ability to fend off liver tumours. They also plan to create rats lacking an immune system gene that causes severe combined immunodeficiency (SCID) in humans missing it.

Moreover, Ying expects transgenic rats to become ever bit as useful as mice for understanding human disease. Knockout rats may even do mice one better.

Some aspects of their physiology, such as their heartbeat, are a closer match to that of humans. It is easier to perform surgery on rats, which are about 10 times larger than mice. And, compared to mice, rats tend to behave more like humans. “I think they’re going to be very useful for neuroscience research,” Ying says.

To help spread the gospel of the rat, Ying’s team has begun teaching other scientists to make their own rat ES cells. Critsner’s centre is happy to supply them.

Image: iStockphoto