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Researchers learn more about failure of some cloned animals

Only 1 percent to 3 percent of animals cloned from adult cells survive to birth; many die mysteriously very early in development, around the time of implantation. A new study suggests that a set of genes important in early development fails to reactivate in adult, or somatic, cell-derived clones, a finding that could help scientists skirt a major roadblock in cloning.

"Most animals cloned from somatic cells fail in all seven species, while animals cloned from embryonic stem cells survive much better," said Professor of Biology Rudolf Jaenisch, a researcher at Whitehead Institute for Biomedical Research and co-author of the new study, which will be published in the April 15 issue of the journal Development. Scientists already knew that among those genes essential to normal embryonic development is the Oct4 gene, which prompts embryos to create pluripotent cells--cells that can form any tissue in the body.

A team of scientists at Whitehead, including Professor of Biology David Page, and the University of Hawaii cloned two types of mouse embryos, one derived from embryonic stem cells and another from somatic cells. Scrutiny of the clones' genetic activity revealed that those made from embryonic stem cells expressed all 10 genes normally, while only 62 percent of somatic cell-derived clones correctly expressed the genes, said Alex Bortvin, a postdoctoral associate at Whitehead and lead author of the paper.

"This finding suggests that other genes that function together with Oct4 in control of early development also might be inefficiently expressed in somatic clones," Bortvin said.

Because the genes are involved in early development, they are turned off in adult cells. But as the debate over embryonic stem cell research continues, scientists must look to adult stem cells for cloning studies that could yield vital information about disease and cell development. So figuring out how to help somatic cell-derived embryos survive to birth is high on the minds of researchers such as Jaenisch and his colleagues.

The researchers are careful to note that while it may be possible to figure out a way to reactivate Oct4-related genes in clones created from somatic cells, that likely won't solve the problem of clone survival.

"There are hundreds of genes that are not correctly expressed in cloned animals," said Jaenisch, whose interest lies in therapeutic cloning designed to study disease. "The issue now is to make cloning more efficient."

A version of this article appeared in MIT Tech Talk on April 9, 2003.

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