The search for treatments for genetic diseases and cancer has taken an important step forward with an advance that should make it simple to create laboratory rats that lack critical genes. Scientists have isolated the most versatile type of stem cells from rat embryos, providing a tool for knocking out genes in the animals to generate powerful models of human diseases.

The master cells will enable researchers to seed rat embryos with tissue in which important DNA is missing in order to breed rats that develop conditions similar to cystic fibrosis, diabetes and human cancers. They can then be studied to improve understanding of these disorders, and to develop new drugs.

Similar “knockout” mice have been available to science since 1989, and have done much to transform medical research: Martin Evans, Mario Capecchi and Oliver Smithies, who developed the key techniques, won the Nobel Prize for Medicine last year.

The latest advance promises further improvements, as rats have more biological similarities with human beings than do mice. Until now, however, the methods used for deriving embryonic stem cells (ES cells) from mice did not work with the larger rodents.

Austin Smith, of the University of Cambridge, who led one of two teams that have now isolated rat ES cells, said the achievement was likely to have a major impact. “The Chinese Year of the Rat heralds a new dawn for this important animal model,” he said. “Rats are the species of choice for investigations of complex physiology, disease and pharmacology. Rat studies have been hindered, however, by lack of the sophisticated genome engineering achievable in mice via ES cells.”

The second team was headed by Qi-Long Ying, of the University of Southern California, who previously worked with Professor Smith while both were based at the University of Edinburgh. “This is a major development in stem cell research,” Dr Ying said. “The research direction of many labs around the world will change because of the availability of rat ES cells. Without ES cells it is impossible to perform precise genetic modifications for the creation of the disease model we want. The availability of rat ES cells will greatly facilitate the creation of rat models for the study of human diseases, such as cancer, diabetes, high blood pressure, addiction and autoimmune diseases.”

In the studies, which are both published in the journal Cell, the research teams have managed to solve the key problem in deriving rat ES cells. ES cells are master cells found in embryos that have the potential to form every type of tissue. When rat ES cells have previously been removed from embryos, however, they have lost this versatile property that makes them so valuable.

Professor Smith and Dr Ying have addressed this by developing a cocktail of two or three molecules that protects the versatility of stem cells. When treated with this, rat ES cells, which previously have failed to propagate, could be grown indefinitely while remaining in their primitive and unspe-cialised master state.

Dr Ying’s team has already begun experiments that seek to use these ES cells to create knockout rats. First, rat ES cells will be genetically modified so that a particular gene of interest is switched off, such as the one that causes cystic fibrosis. These will then be injected into normal rat embryos.

These embryos will be implanted into a surrogate mother, growing into “chimera” rats that have some normal cells and others that lack the gene in question. When these rats breed, the gene will be missing in some of their descendents. Dr Ying said: “This will have a major impact on the future of biomedical research.”

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