ABC News
How is that
possible? Mutant mice — lots of them.
If a consortium
of geneticists have their way, there will soon be a mutant mouse
bred for every single gene in the genome. Mice and people are
thought to be nearly identical in genetic makeup and the tiny
lab mammals have proven vital for understanding the roles of genes.
But considering
the genome sequence consists of between 26,383 and 39,114 genes,
the vision could entail maintaining nearly 40,000 slightly altered
mice in laboratories around the world.
Thousands
of Mice Yet to Mutate
"The
biggest problem for the mouse consortium is what do we do with
all the mice," says David Beier, a geneticist at Harvard's
Brigham and Women's Hospital, and a coauthor of a proposal outlined
in this week's Science to create such a mouse bank. "How
will we handle them, how will we make them available to investigators?"
For nearly
100 years, lab workers have manipulated the genetic make-up of
mice to understand the workings of human development, disease
and birth defects. The lab work has led to the understanding of
several critical genes, including ones thought to contribute to
Alzheimer's, Down's syndrome and epilepsy.
But, in terms
of understanding the entire genome, the work has only begun. So
far scientists have determined the function of fewer than 5,000
genes. The release of the human genome sequence, complete with
the genes' locations and, in some cases, proposed functions, is
sure to speed up research.
"The
genome turns our research on its head," says Miriam Meisler,
a geneticist at the University of Michigan. "It means we
no longer have to isolate a gene. We can now concentrate on the
most interesting thing — which is function."
Ways to
Mutate a Mouse
To detect
the function of a gene using mice, researchers use one of two
main methods. One is to introduce mutations into a mouse by exposing
it to a chemical known to cause random mutations. Scientists then
study any visible changes in the mouse's condition and hunt for
the genes that have been mutated.
The second
method is to target a specific gene, mutate it, and then see how
the mouse is affected.
"We will
most likely have to create many more than 30,000 mutant mice,"
Meisler points out. "Because many mutations aren't necessarily
from deactivating the gene, but from subtle changes in the gene."
The effort
to generate possibly hundreds of thousands of mutant mice will
be shared among at least 10 major mouse research centers already
in existence around the world. Then data from each of these centers
will be placed under a single umbrella — and a single Web
site.
"The
idea is to bring all of these groups under one roof and coordinate
the dissemination of data," explains Beier.
Not all groups
are particularly excited about the idea. Peter Wood of People
for the Ethical Treatment of Animals says the likely results of
the project cannot possibly justify the means.
"We believe
the manipulations of animal life in this manner is cruel and unethical.
And this is just another empty promise that the research industry
has forcing the public to accept for decades," Wood says.
Freezing,
Rather Than Housing
There may,
however, be ways of reducing the need for housing an actual mouse
for every mutation. Some research centers have refined ways of
freezing mouse sperm and embryos that contain a certain genetic
lines. So genetic information can be stored in freezers, rather
than by housing and feeding generations of living mice, which
live between one and two years.
"Mouse
costs have been zooming up and represent a large fraction of research
budgets," says Beier. "Bedding and water and food all
needs to be constantly monitored."
Even if the
vision of a complete mutant mice bank is completed in the near
future, as scientists hope, Beier points out the tiny mammals
may not hold all the answers for human genetic disorders.
"Mice
and people are certainly more alike than they are different,"
says Beier. "But there are significant differences."
For example,
of 20 compounds known not to cause cancer in humans, 19 do cause
cancer in mice. And a common drug, aspirin, is largely harmless
to people but is known to cause birth defects in mice. In the
major paper released in this week's Science, lead author Craig
Venter of Celera Genomics estimates mice and people differ by
about 300 genes.
But even finding
differences between mouse and human genetics, says Beier, can
shed light on understanding the underlying biology of both animals.
This kind
of science, says Beier, "has a very large 'cool factor.'
You can go into the lab and immediately find big results."
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