|
Fat
Agouti and normal mice.
|
Scanning
electron micrograph of deoxygenated
red blood cells from transgenic
mouse exhibiting typical sickle-cell
characteristics. |
Although they differ dramatically
in size and appearance, mice and humans
are very similar genetically. For
this and other reasons, the mouse
is the most widely used model for
studies of human gene function. Many
such studies have been funded by the
Office of Science and predecessor
agencies. In the 1940s, Bill and Lee
Russell started a mouse genetics program
at Oak Ridge National Laboratory,
where they set up the "mouse house,"
which became one of the world's largest
colonies of experimental mice (it
houses some 70,000 mice today). Their
studies of genetic mutations led to
a number of discoveries, as in 1979,
when Bill Russell found that the laboratory
chemical ethylnitrosourea is the most
potent mutagen ever tested in mice,
making it a useful research tool.
In 1992, Richard Woychik and colleagues
at Oak Ridge showed that a long-studied
gene for a color mutation of the mouse
coat, known as the Agouti gene, is
related to a human gene that contributes
to obesity and insulin-dependent diabetes.
More recently, Chris Paszty and Edward
Rubin of Lawrence Berkeley National
Laboratory worked with other scientists
to genetically engineer the first
strain of mice to mimic fully all
the symptoms of human sickle cell
disease, thus offering a way to test
experimental treatments.
Scientific Impact:
Research on mice has contributed significantly
to the field of mammalian mutagenesis,
and thus to the practice of genetic
risk assessment. For example, ethylnitrosourea
has become a standard tool for studying
gene function and mechanisms of mutagenesis.
Social Impact: Based
on mouse studies, scientists have
developed new leads to treatments
for obesity, insulin-independent diabetes,
Down syndrome, liver cancer, kidney
disease, leukemia, sickle-cell disease,
and many other conditions. In addition,
research on genetic mutations in mice
led to reductions in permissible levels
of occupational exposure to radiation.
Reference: Science
278:876-878 (1997)
Nature Genetics 11:33-39
(1995)
Mammalian Genome 11:1024-1029
(2000)
Russell, W. L., E. M. Kelly, P. R.
Hunsicker, J. W. Bangham, S. C. Maddux,
and E. L. Phipps, "Specific-locus
test shows ethylnitrosourea to be
the most potent mutagen in the mouse,"
Proc. Natl. Acad. Sci. USA
76:5818-5819 (1979).
Bultman, S. J., E. J. Michaud, and
R. P. Woychik, "Molecular characterization
of the mouse agouti locus," Cell
71:1195-1204 (1992).
URL: http://www-gsd.lbl.gov/GSindex.htm
http://bio.lsd.ornl.gov/mgd/home.htm
Technical Contact:
Dr. David Thomassen, Life Sciences
Division, Office of Biological and
Environmental Research, 301-903-9817
Press Contact: Jeff
Sherwood, DOE Office of Public Affairs,
202-586-5806
SC-Funding Office:
Office of Biological and Environmental
Research |