( s in an otherwise normal animal. Mosaic...)Mosaic mouse technique offers a powerful new tool to study diseases and genetics

Geneticists have been using mosaic fruit flies for decades. In the early 1990s, scientists developed a more efficient technique that allows researchers to control when and where mutant cells are generated in the fly's body. However, scientists have had a much more difficult time designing mosaic vertebrates, such as mice. The mouse has long been considered an ideal laboratory model for studying human development and disease, primarily because mouse DNA and human DNA are remarkably alike.

The MADM technique, which Luo and his colleagues developed for mice, works on the same principal as the method currently used to create mosaic fruit flies. The researchers begin with two embryonic stem cells whose chromosomes have been engineered to carry two inactivated segments of a green fluorescent protein molecule. Mice derived from these embryonic stem cells are mated to each other. As their offspring grow, the cells in their body begin to divide--a normal process that results in the duplication of each chromosome. Before cell division is complete, a special enzyme causes the exchange, or recombination, of the two engineered chromosomes. If one of those chromosomes contains a bad copy (mutation) of a gene, the recombination event could cause an offspring to inherit two bad copies of the gene, which would result in a mutant cell. This process simultaneously activates the green fluorescent protein, which turns the mutant cell green.

"If there is no recombination, there are neither green nor mutant cells," Luo explains. "So even if only one cell turns green, we know it has to contain the mutated gene of interest."

In their study, the Stanford team focused on the cerebellum, the part of the brain whose main function is to coordinate motor activity and maintain balance. The researchers used MADM to study the development of cerebellum granule cells, which are the most abundant cells in the brains of mice an
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Source:Stanford University