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5-Animals: Study sheds light on why cloning so often fails

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TITLE:  Study Sheds Light on Why Cloning So Often Fails
SOURCE: Reuters Health, by Jacqueline Stenson
DATE:   Apr 4, 2003

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Study Sheds Light on Why Cloning So Often Fails

NEW YORK (Reuters Health) - The vast majority of attempts at animal
cloning are a failure and it may be because certain genes necessary for
early development are not activated in the process, new study findings

In the cloning procedure that created Dolly the sheep and other cloned
mammals, researchers extract the nucleus of an adult cell from an animal
that is to be cloned and insert it into an egg that has been stripped of
its own nucleus. If everything goes as planned, a very early embryo known
as a blastocyst results, is transferred into the womb of a female and
grows into a clone of the adult.

But the process fails the vast majority of the time. In mice, only 1 to 3
percent of blastocysts develop to full-term offspring, and fewer survive
to adulthood, said Dr. Rudolf Jaenisch, a professor of biology at the
Whitehead Institute for Biomedical Research and the Massachusetts
Institute of Technology (news - web sites), both in Cambridge.

By comparison, he said, up to a third of clones created using an embryo-
derived stem cell instead of an adult cell survive to birth.

The question is what accounts for the difference.

Embryonic stem cells are derived from a developing embryo and have the
ability to grow into any cell type in the body. To date, researchers have
isolated embryonic stem cells from mice and humans only, Jaenisch noted.

In a new study published in the journal Development, Jaenisch and
colleagues compared normal mouse blastocysts to those cloned from adult
cells or embryonic stem cells.

The researchers were looking for the expression of a gene called Oct4,
which is essential for normal embryonic development, and 10 other genes
that appear to function similarly.

All 11 genes were properly expressed in the normal blastocysts and the
ones cloned from embryonic stem cells, results showed. But among the
blastocysts cloned from adult cells, just 62% expressed all 11 genes.

"This argues that the faulty reprogramming that one sees in cloning is
caused by the inability of the clone to activate those silent genes,"
Jaenisch told Reuters Health.

These genes, already at work in a normally developing embryo or one
cloned from embryonic stem cells, have long been inactivated in adult
cells, he explained.

The findings raise the issue of whether researchers can find ways to turn
these inactivated genes back on, he said.

But this research is just part of the story of how to more efficiently
clone animals, Jaenisch noted, because hundreds of genes are not
correctly expressed in clones, creating problems during development and
throughout life.

Scientists are seeking to clone healthy animals for a variety of reasons.
Some wish to create herds of animals that have been genetically altered
to produce therapeutic milk or organs for human transplant, for example,
and others are hoping to save endangered species.

SOURCE: Development 2003;130:1673-1680.