- NEW YORK (Reuters Health)
- Researchers have discovered a possible reason for why so few cloned embryos
mature into healthy animals.
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- The study, which looked at the genetic make-up of certain
organs in cloned mice, found that as many as one in 25 genes might be abnormal
in a clone's placenta, according to the report published in the early edition
of the Proceedings of the National Academy of Sciences.
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- The researchers suspect that the abnormalities are a
result of the cloning process itself, Dr. Rudolf Jaenisch, a professor
of biology at the Whitehead Institute for Biomedical Research at the Massachusetts
Institute of Technology in Cambridge, said in an interview with Reuters
Health.
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- Jaenisch and his colleagues decided to look at the cloning
process because so many cloned embryos die either before they are born
or shortly after birth. Among other symptoms, a clone that doesn't make
it may have respiratory problems and an enlarged and dysfunctional placenta.
Mouse clones that do survive can be plagued with obesity, frequent pneumonia,
liver failure and short life spans, Jaenisch explained.
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- In the new study, Jaenisch and his colleagues decided
to closely scrutinize the genetic development of placentas and livers in
cloned newborn mice.
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- When clones are made, scientists take the cell nucleus
from an animal or embryo and put it into the "shell" of an egg,
or oocyte. In its new cellular home, the nuclear material reprograms itself
to become more like the actual nucleus of an oocyte. With the right spark
of electricity, the egg's reproductive machinery can be jolted into motion
to divide and grow into an embryo.
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- But researchers are now discovering that things can go
wrong with the initial reprogramming of the transplanted nucleus.
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- "The nuclear transfer procedure interferes with
normal reprogramming and this leads to multiple genes being not correctly
expressed," Jaenisch said. "Our data also show that this dysregulation
of genes depends on the nuclear transfer per se as well as the type of
donor nucleus--that is, many genes are dysregulated in all clones, whether
they are from an embryonic stem cell or (adult animal) donors. This reveals
that the nuclear transfer procedure, regardless of donor nucleus, leads
toproblems."
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- To get a better idea of how well the cloning process
was working, Jaenisch and his colleagues scrutinized more than 10,000 genes
in the cloned mouse placentas. Approximately one in 25, they found, were
abnormally expressed. When the researchers looked at genes from clone livers,
they also found significant numbers of abnormalities, though not as many
as in the placentas.
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- Ultimately, Jaenisch believes that even surviving clones
are genetically damaged.
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- "I believe that all clones may have abnormalities
but to different extents," he said. "The ones that survive have
less severe abnormalities and that is why they survive. We have seen abnormal
gene expression in all newborn clones."
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- The new research may have turned up fundamental flaws
in the way scientists now create clones.
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- "Reprogramming errors may reveal a serious biological
barrier to cloning," Jaenisch said.
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- SOURCE: Proceedings of the National Academy of Sciences
2002;10.1073/pnas.192433399.
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