Devil’s Lapdog Gets Its Due: The lab rat bares its DNA to biologists

Overshadowed in scientific circles for the past few decades by its smallish cousin the mouse, the rat is back in the limelight. This week, biologists announced that they have deciphered the full DNA sequence of the standard lab rat, setting the stage for a new flurry of biomedical research on this rodent and providing insight into mammalian evolution.

People and rats have a long history together, not all of it happy. The Chinese made the animal the first sign of their zodiac, but others have called it the devil’s lapdog and blamed it for spreading the plague.

Scientific studies of laboratory-raised rats began in the early 1800s, many decades before researchers began to seriously investigate mice. Since then, researchers have identified or bred hundreds of rat strains that suffer conditions mimicking human diseases such as high blood pressure, obesity, diabetes, cancer, and arthritis.

The mouse’s genes, however, proved easier to study and modify, so scientists deciphered the entire mouse DNA sequence, or genome, before turning to the rat. “The mouse has gotten a lot of good press, but the rat really is the workhorse of biomedical research,” says Richard Gibbs of Baylor College of Medicine in Houston.

In the April 1 Nature, Gibbs and an international team of more than 100 scientists unveiled the genome of the albino laboratory strain of the rat called brown Norway (Rattus norvegicus). Also, the April Genome Research features about 30 papers in which different groups of the same researchers analyze the rodent’s DNA in various ways.

According to the Nature report, the rat genome contains less DNA than the human genome does but slightly more than the mouse genome. All three species possess similar numbers of genes, perhaps as few as 25,000, the scientists say.

Almost every known human-disease gene has a rat counterpart, Gibbs and his colleagues report. Other researchers, using a preliminary version of the rat genome, have already identified previously unrecognized human-disease genes. Last year, for instance, investigators found a rat gene that causes a kidney disorder in the animals and subsequently confirmed that mutations in the human version of the gene produce a similar disease in people.

The rat genome “has already stimulated some exciting advances,” says Stephen Mockrin of the National Heart, Lung, and Blood Institute in Bethesda, Md.

When scientists unveiled the mouse genome last year, they suggested that the rodent’s DNA had changed much more than the human genome had since the two species diverged from a common ancestor (SN: 2/22/03, p. 122: Available to subscribers at Mining the Mouse). Comparisons of rat and human DNA indicate that the rat’s genome has also developed in the fast lane. “The whole rodent lineage seems to be evolving more quickly” than the human one, says Gibbs.

The rat is the third mammal—after people and mice—to have its DNA thoroughly sequenced. The new information could enable researchers to determine which stretches of DNA are common to all mammals and which are specific to rodents. Presumably, any gene shared by all three species performs some vital function. Otherwise, evolution would have scrambled it in at least one species.

“Having [the genomes of] three mammalian species really improves the ability to do comparative genomics and find new genes,” says Michael Gould of the University of Wisconsin–Madison.

Last year, Gould and his colleagues reported a technique that can inactivate a gene in rat embryos, a tool that mouse researchers have long had. It enables biologists to probe the function of newfound genes

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