rampagaing mice made more human
- From: "outrider" <outrider@xxxxxxxxxxxxx>
- Date: 9 Jul 2005 09:34:22 -0700
Rampaging mice made more human
By CAROLYN ABRAHAM
Wednesday, July 6, 2005 Updated at 8:57 AM EDT
>>From Wednesday's Globe and Mail
A breakthrough experiment has used a human gene to turn vicious mice
into very gentle creatures -- holding out the prospect of doing
similarly sweet things to violent people.
Scientists at the University of British Columbia's Centre for Molecular
Medicine and Therapeutics created a strain of extremely vicious lab
mice three years ago after accidentally deleting a gene that affects
brain development.
The mutant mice were so aggressive they killed their mates, chewed
their siblings' tails and even attacked their lab handlers.
The unanswered question was whether the human form of the gene also
plays a role in aggression in people. The new research now suggests
that it does.
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By giving mutant mice embryos the human version of the gene they were
missing, the UBC team found the nasty rodents grew into a rather nice
strain instead.
As such, the experiment raises the possibility of designing a gene
therapy to counter aggression -- as well as the eerie spectre of
enhancing it.
More immediately, it means mice can act as models to study human genes
involved in abnormal behaviour and psychiatric disorders.
"Mice have been used to study human genes for cancers and other
diseases lots," said UBC geneticist Elizabeth Simpson, senior author of
the report published today in the Journal of Neuroscience. "But this is
the first time [a human gene] is being used in a mouse to study the
brain and behaviour."
After UBC researchers created the so-called "fierce mice" in 2002, they
searched the human genome looking for a gene with a sequence that
closely matched the one missing in their mutant mice.
That gene, Dr. Simpson said, called NR2E1, is found on a region of
Chromosome 6 in humans that has been repeatedly associated with bipolar
disorder, a serious medical illness resulting in dramatic mood swings.
The gene itself produces molecules that regulate other genes,
suggesting it plays many roles in the human body, including those
involved in brain development and function. That a similar version
exists in the mouse suggests the gene is a primitive one, passed down
to mice and people from a common ancestor many millenniums ago.The team
ordered the human gene by mail and then inserted it into a mouse embryo
at the earliest stage of development. This way the new human gene would
be absorbed into the animal's genome as the embryo cell divided and
grew.
Mice without any form of the NR2E1 genes were, as predicted, violent.
Those with two copies of the mouse gene were normal, as were those with
one mouse copy and one human copy. But most surprising was that mice
that carried only the human NR2E1 gene also appeared to be normal.
"They were indistinguishable from mice in the wild," Dr. Simpson said.
The researchers also were careful to control for environmental forces
that could result in different behaviours, feeding all strains the same
food, in the same kinds of cages and offering them the same social
interactions: "The only thing that differed in these mice was their
genetic constitution."
University of Lethbridge neuroscientist Bryan Kolb, who studies early
brain injuries in rats, said the experiment amazed him.
"This [paper] is saying that by interfering with the cells that build
the brain you can get this profound effect in behaviour," Dr. Kolb
said. "The fact that a single gene is controlling this is astounding."
Dr. Kolb, a professor with the university's Centre for Behavioural
Neuroscience, said he could envision all sorts of experiments that
could flow from this kind of human-animal model.
Yet Margaret Somerville, founding director of the McGill Centre for
Medicine, Ethics and Law, said concerns already have been raised that
some country or group might try to use such research to design perfect
soldiers whose genes are manipulated to make them fearless killers.
A field of "neuro-ethics" has already sprung up to discuss issues
around genes, free will and criminal law, she added.
"We've got to be very careful here," Dr. Somerville said, "in thinking
we understand more than we actually do understand."
Dr. Simpson acknowledged the report may leave people uncomfortable
because it highlights the power of biology in shaping behaviour. But,
she said, "For some reason we think the brain is different from your
liver, yet we should see the brain as no different than any other part
of our body."
Although genes do not tell the whole story, she said, they can
illuminate an important aspect of it. She noted that Huntington's
disease, a neurodegenerative disorder that can have an impact on
speech, movement and thought, was once seen as a psychiatric disorder
before scientists realized the condition stems from a mutated gene.
fairuse
http://www.theglobeandmail.com/servlet/story/RTGAM.20050706.wxmice06/BNStory/specialScienceandHealth/
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