Writing in the May 6 edition of the journal Cell, researchers from Stanford University describe a streamlined method for creating a "genetic mosaic mouse"--a rodent whose body is genetically engineered to produce small clusters of cells with mutated genes.
The new technique, called Mosaic Analysis with Double Markers (MADM), was developed in the laboratory of Liqun Luo, professor of biological sciences at Stanford who was recently named an investigator with the Howard Hughes Medical Institute.
"With MADM, you can look at a tiny subset of cells and study gene function at a very high resolution," says Luo, who also is affiliated with the Neuroscience Institute at the Stanford School of Medicine. "Our method can be used to study a variety of tissues, such as the skin, heart and nervous system."
Mosaics are designed to give researchers an opportunity to observe what happens when a specific gene is removed from a small cluster of cells in a living animal. With MADM, cells carrying an altered gene of interest actually turn green for easier observation.
"We use a green fluorescent protein," Luo says. "So now if you mutate a gene, you'll know in which cell the normal gene is lost. For example, if you delete a tumor suppressor gene, the green cells will proliferate, and you can actually study the tumor's progression. If you can image these cells in a live animal, you can potentially watch the tumor grow."
Luo points out that MADM is more precise than the widely used "knockout mouse" technique, in which a gene of interest is removed ("knocked out") of every cell in the animal's body. The knockout method can have unwanted, deleterious consequences for the mouse and the experiment, Luo adds, whereas MADM acts more like a scalpel, creating a handful of mutant cell