French researchers first to clone rats

Friday, September 26, 2003

WASHINGTON -- While people all over the world try to get rid of rats, researchers in France have cloned them.

The scientists overcame a quirk in rat physiology to produce genetic duplicates for use in medical research.

Led by researchers at the National Institute of Agricultural Research scientists cloned both male and female rats and then mated them and produced normal, healthy pups. A report on the study appears today in the journal Science.

Experts hailed the achievement as an important advance in medical research because laboratory rats with special genetic changes can be developed and used to test drugs and other therapies that may benefit human patients.

While wild rats worldwide are considered vermin because they carry disease and can spoil food stores, white laboratory rats are among the most frequently used animal models for human disease research. Genetically manipulated laboratory rodents are highly prized by scientists because they provide a unique opportunity to probe biological processes that cannot be studied in humans.

To clone the animals, the researchers had to expose rat eggs to an inhibitor protein that halted activation of the eggs. Previous attempts had failed because the eggs mature so rapidly that the experimenters don't have time to manipulate the nucleus. By halting the activation, scientists could remove DNA from the eggs and replace it with DNA from a mature rat cell, a technique called somatic cell nuclear transfer.

Cloned pairs mated

Alexandre Fraichard, chief executive officer of a Lyon, France, biotech company, genOway, and a co-author of the study, said the researchers first produced two male rat pups. In a second round of cloning, they got two female pups. The pairs were later mated and produced normal, healthy young.

Fraichard said the researchers first removed the nucleus from eggs that had been taken from female rats. Into these eggs, the scientists inserted DNA removed from mature cells that had been extracted from rat embryos. This resulted in 129 live embryos that were allowed to progress to the two-cell stage, a very early point in development.

The embryos were then divided and 64 were placed into the womb of one female rat and 65 into another. From this, one of the females gave birth to three male pups, one of which later died. The two survivors were genetically identical to the donor cells from the original rat embryos.

Fraichard said the technique was repeated and this time produced two healthy females.

All the cloned rats "developed normally into sexually mature animals," he said. Two successive healthy generations have now been produced by mating the clones, said Fraichard.

Robert Lanza, medical director of Advanced Cell Technology, a cloning lab in Worcester, Mass., praised the achievement, saying that being able to clone rats will enable medical researchers to genetically tailor the laboratory animals for studies of specific disorders that affect humans.

"Nobody up to now has had any success in cloning the rat," said Lanza. "This is extremely important. We now have the potential to create all sorts of animal models (to study diseases.)"

Lanza said that his lab had failed to find the precise technique needed to clone rats. He said that the reproductive systems of each mammal is slightly different and successful cloning can be achieved only after many experiments and failures.

So far, the mammal clones include sheep, cows, pigs, cats, mice, mules and horses. No primate clones have been scientifically demonstrated. One organization said it cloned a human, but that claim has not been verified and is generally dismissed.

Fraichard said the next step of the French team is to put a human gene into a family of rat clones and then use the animals to study therapies against diseases linked to that gene. He said the first gene would be associated with an inherited metabolic disorder in humans.

GenOway holds the patent for the technique used to clone rats, and Fraichard said he and his company hope to profit as the result of the research reported in Science.

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