File Photo: All the participant mice in the cloning process are shown in this photo released by ProBio America, Inc. after 22 mice were cloned at the University of Hawaii. Top left is the egg donor, top right is the nucleus donor, the white mouse lower middle is the surrogate mother and the two brown brown mice on either side of her are the cloned offspring of the nucleus donor. AFP PHOTO/PROBIO AMERICA
Teruhiko Wakayama of the Rockefeller University in New York and his team say the mice in their experiment appeared healthy. But it became harder to clone them with each successive generation.
Only one mouse was produced in the sixth generation despite massive effort. And this lone clone was eaten by its foster mother. "Either it was sick and died or the foster mother didn't like it and destroyed it," he says.
Cloning is based on a technique known as nuclear transfer. The nucleus of a donor cell is fused with an egg stripped of its own genetic material. The result is an animal that is genetically identical to the animal from which the donated nucleus came.
Wakayama and his team first hit the headlines two years ago when they cloned the mouse Cumulina, the first clone produced from an adult animal since Dolly the sheep.
They also announced the remarkable feat of serial cloning. By using donor cells from each successive generation, they produced four generations of clones. In their new report, they report for the first time that they could not produce mice past the sixth generation.
They explored two possible reasons. First, the end of chromosomes or "telomeres" have been seen to shorten in some cloned animals. This erosion could make viable offspring impossible after serial cloning. Secondly, they suspected that the general health of the clones might deteriorate with each set of new offspring.
But neither one of these possibilities seems to be true. In fact, the mouse telomeres seem to grow slightly with each generation. And all the clones could navigate mazes and pass other cognitive tests with flying colours. They also aged gracefully - one fifth generation mouse is alive and well in mouse middle age, 18 months.
Wakayama's team continues to search for some hidden flaw. "Our results suggest clones are accumulating some abnormality," he says. The fact that the final animal was eaten by its foster mother might suggest the defect is obvious to rodent senses, if not human testing.
Source: Nature (vol 407, p 318)
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