Chromosome transplant in mice could provide clue to Down's syndrome illnesses
- From: "Cowboy" <msbuckaroo@xxxxxxxxxxx>
- Date: 23 Sep 2005 16:02:04 -0700
http://www.guardian.co.uk/medicine/story/0,11381,1576717,00.html
Chromosome transplant in mice could provide clue to Down's syndrome
illnesses
· Studies will help scientists tease out problem genes
· Critics say boundaries being pushed too far
Ian Sample, science correspondent
Friday September 23, 2005
Scientists have successfully transplanted human chromosomes into mice,
a first that promises to transform medical research into the genetic
causes of disease. The mice were genetically engineered to carry a copy
of human chromosome 21, a string of about 250 genes. About one in a
thousand people are born with an extra copy of the chromosome, a
genetic hiccup that causes Down's syndrome.
Genetic studies of the mice will help scientists to nail down which
genes give rise to medical conditions which are prevalent among people
with Down's syndrome, such as impaired brain development, heart
defects, behavioural abnormalities, Alzheimer's disease and leukaemia.
Medical researchers yesterday hailed the work as a "tour de force", but
critics accused the team of pushing the boundaries of genetic
manipulation too far and blurring the distinction of what was
biologically human.
Elizabeth Fisher at the Institute of Neurology and Victor Tybulewicz at
the National Institute for Medical Research in London spent 13 years
perfecting the technique which is reported in the journal Science
today.
To create the mice, the team first extracted chromosomes from human
cells and squirted them on to beds of stem cells taken from mouse
embryos. Any stem cells that absorbed human chromosome 21 were injected
into three-day-old mouse embryos which were then re-implanted into
their mothers. The newly born mice carried copies of the chromosome and
were able to pass it on to their own young.
"By adding the chromosome, we have mice that show nearly all of the
characteristics of Down's syndrome in humans," said Dr Fisher. "It
means we can tease out the genes that give rise to the different
aspects of Down's syndrome, because we know we've got the right genes
in there."
According to Dr Tybulewicz, genetic tests on the mice, which will
systematically knock out different genes on the transplanted
chromosome, will help identify which gene or genes cause each of the
symptoms common to people with Down's syndrome. "This should illuminate
which genes lead to heart defects, the higher risk of leukaemia and
early onset Alzheimer's," he said.
Peter Scambler, a molecular geneticist at the Institute of Child Health
in London, said: "This is a technical tour de force. It's difficult to
envisage how one could otherwise tackle something as complex as Down's
syndrome, because we can't go around creating human embryos with the
condition."
Steve Brown, director of the Medical Research Council's mammalian
genetics unit, said: "This will tell us a lot about which genes are key
to the myriad abnormalities we associate most with Down's syndrome. We
are taking a step forward in the tools we have to investigate the
genetic basis of these conditions."
But according to David King, of the pressure group Human Genetics
Alert, the potential breakthrough comes at too high a cost. "Creating
organisms with whole chromosomes from another species is genetic
engineering taken to another level.
"Before, researchers have said they're not making big changes because
they're only inserting the odd gene into animals. If you're talking
about creating something with a whole human chromosome in it, you have
to ask is this really a mouse any more? Is it starting to be a new
species, a hybrid between a mouse and a human? If more chromosomes are
put in, are we going to have to start giving these things pseudo human
rights?"
Dr King said the research could lead to technologies that would allow
humans to be genetically engineered. "Once Britain has a clear ban on
human genetic engineering, I'll be much happier for scientists to do
these studies with mice. But they're developing techniques that could
be applied to human beings and, in essence, that leads to a new form of
eugenics," he said.
Dr Fisher said the transferring of a chromosome was merely a more
effective way of swapping large numbers of genes into an animal to
benefit medical testing. "We're not trying to humanise mice, we're
trying to tease out the genetics of a very complex disorder."
Dr Tybulewicz added: "There's nothing more obviously humanlike about
these mice than any others. If you were to see them, you'd not be able
to tell they are different to a normal one."
Carol Boys of the Down's Syndrome Association said she welcomed the
research if it would lead to an improvement in the lives of people with
Down's syndrome. "Any research that could lead to a greater
understanding of why people with Down's syndrome are more susceptible
to certain medical conditions is important. However, this research does
not herald a 'cure' or a 'treatment' for Down's syndrome."
Footnotes
Chromosomes
Humans have 23 pairs of chromosomes, each a continuous strand of
tightly coiled DNA, which together contain our entire complement of
genes. The two sexes share 22 of the pairs, but the 23rd pair, the sex
chromosomes, differ, with women having two X chromosomes and men having
one X and one Y chromosome.
Down's syndrome
People born with three copies of chromosome 21 instead of the usual two
develop Down's syndrome. About 60,000 people have it in the UK. People
with Down's syndrome typically have craniofacial abnormalities,
impaired brain development and are at a greater risk of leukaemia,
heart defects and Alzheimer's disease. They can expect to live to
between 40 and 60.
Stem cells
In the first few days of their existence, embryos contain stem cells
that can form any of the tissues needed to make an entire organism,
including bone, skin, muscle or nervous tissue.
Knock out
One of the most common ways to find out what a gene does in an animal
is to knock it out. When scientists knock out a gene they silence it,
so that it is in effect missing from the animal. Comparing animals with
and without the gene helps reveal the role of the gene.
Eugenics
The science of using controlled breeding to increase the occurrence of
desirable heritable characteristics in a population.
Guardian Unlimited © Guardian Newspapers Limited 2005
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