- WASHINGTON (Reuters) - British researchers said on Monday they had
found a gene that seems to regulate how fast mad cow disease can develop
in mice, and perhaps in humans as well. There are only two versions of
the gene, one fast and one slow, they reported in the journal Nature Genetics.
Although they worked in experimental mice, they said the results might
explain why some people have fallen victim to a new strain of the deadly
brain disease. Jean Manson and colleagues at the Institute of Animal Health
in Edinburgh were building on evidence that an animal's genes determine
how susceptible it is to such diseases, which include scrapie in sheep,
bovine spongiform encephalopathy (BSE or mad cow disease) and Creutzfeldt-Jakob
disease (CJD). Sheep are known to have a gene that influences the course
of the disease. Although they must be infected with a mutated version of
a prion, a brain protein blamed for carrying the disease, the gene clearly
makes them more susceptible. Manson's group worked with mice injected with
an experimental strain of BSE. They genetically engineered the mice so
they had one or the other version of the prion gene -- which exists naturally
because prions, unless mutated, are a normal brain protein. The difference
between the two genes is very subtle -- only two amino acids are affected.
The mice that had the ``fast'' version of the gene developed BSE twice
as quickly as those that had the ``slow'' version. ``In a formal way, they
proved that it is the gene that codes for the prion protein in the mice
that controls the incubation period,'' Dr. Chris Bostock, spokesman for
the Institute, said in a telephone interview. He said the findings would
vary depending on which strain of disease was used, but in this case the
``slow'' mice developed disease in 250 or so days, while those engineered
to have the ''fast'' version'' developed BSE in 133 days. Bostock said
the findings might translate to people. CJD naturally occurs in one in
a million people, but a new version linked to BSE was identified two years
ago and has killed or infected 23 people in Britain. Every one of the 23
had the ``fast'' version of the prion gene, Bostock said. What is not clear
is whether having the slow version means infected people will develop the
new variant of CJD more slowly, or whether it makes the incubation period
so long that they will never develop it at all, Bostock said. ``These mutations
all exist as natural mutations in the population,'' he added. About 90
percent of the population has a ``fast'' version of the prion gene. Of
these, about 35 percent have two versions of the gene, while 55 percent
of the population carries one ''fast'' and one ``slow'' gene, Bostock said.
Only about 10 percent carry two copies of the ``slow'' gene. Having two
copies of a gene generally strengthens its effects. The next step is to
see precisely what the effects of these mutations are on the prion, Bostock
said. ``There are clearly other genetic elements present that you can identify
have an effect,'' he added. ``We are very interested to find out what these
are.'' CJD normally has an incubation period of decades. The victims of
the new strain of CJD must have been infected in the mid-1980s, when BSE
was rife in British herds. Researchers do not know whether the 23 victims
are the leading edge of an epidemic, or unfortunate but rare cases. Knowing
more about what affects the incubation period of the new strain will help
predict whether an epidemic is yet to come.
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