The researchers will employ a genetic technique known as genome-wide mutagenesis. A chemical called ENU (N-ethyl-N-nitrosourea) is used to create a broad spectrum of random mutations, single base pair changes in DNA, that are passed on to subsequent generations.
"For many diseases and behaviors, humans and mice are very similar the corresponding genes have similar functions," said Takahashi, who also is an investigator in the Howard Hughes Medical Institute. "In humans, more than 35 percent of the genes have unknown functions, and a good number of these genes are likely to be important for the function of the brain. This gives us an opportunity to discover new genes critical to the nervous system in the mouse, which will contribute to our understanding of the human system."
The approach being used by the center, called forward genetics, in which the animals behavioral change leads to identification of the responsible genes, has been shown to be powerful and productive. Once there is evidence of a single gene mutation, scientists can identify the gene using positional cloning.
Takahashis laboratory was the first to use the ENU technique to identify a mouse with a behavioral problem, in this case a problem with its circadian clock. The use of forward genetics led to the identification in 1994 and the cloning in 1997 of the mammalian circadian gene, Clock. Last year, the lab used similar methods to identify casein kinase I epsilon as the first enzyme target for circadian rhythms in mammals.
Using a battery of high-throughput tests, Northwestern researchers first will screen the mice for specific behaviors, such as response to light and the timing of activity and rest, and identify those that fall into one of the five areas of interest. Researchers at all four collaborating institutions will then study the mice that fall into their a
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Contact: Megan Fellman
fellman@northwestern.edu
847-491-3115
Northwestern University
16-Apr-2001