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).

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