News
Manufacturing Mice
[Continued]
Living Test Tubes
The tiny rodents have proven themselves to be invaluable living test tubes, within which researchers have rewritten or erased specific bits of life's genetic blueprint, as they try to understand such mysteries as how cancer cells proliferate out of control, or how subtle biochemical breakdowns cause abnormal behaviors.
Dozens of medical center tabs use the genetically altered mice to study hundreds of genes.
Gene-altered mice are by far the animal of choice among the small zoo of creatures scientists use to study the genetic basis of disease, says Gordon Hammes, vice chancellor for medical center academic affairs.
"There's just no other way to do these studies," he says. "While bacteria or plants do have biochemical similarities to humans, when you want to find out the physiological effects of genetic mutations, or the genetic basis of disease, you have to use animal models. Of course, the mouse is not the most humanlike animal, but they're ideal in other respects. You can breed them easily and get them in large quantities, and they're relatively inexpensive."
The engineered mice come in two basic models—transgenic and knock-out. Transgenic mice, developed about 15 years ago, are produced by inserting a foreign gene into the mouse DNA to assay its effect. Knockout mice, however, are made by disrupting a specific gene, to figure out how important it is in the animals' function.
Says transgenic facility director Joseph Nevins: "In the past we might have done these assays in cell cultures, but now we can do them in the context of the whole animal and its development. These experiments are of enormous value, because now we can do a specific alteration of a gene and ask what its consequence is in a whole mammalian organism."
Knockout mice are by far the most frequently created animals, says Nevins, a Howard Hughes Medical Institute Investigator and chair of the genetics department. Knockouts constitute about 80 percent of the facility's denizens—making the formal name "Transgenic Mouse Facility" a bit of a misnomer, he says.
Master of Mousemaking
The recipe for a mouse, whether transgenic or knockout, begins with a gene isolated and copied in bacteria cultured by the scientists studying the gene. Next, these copied genes must be insinuated into living mouse cells, a high and delicate art practiced by facility coordinator Cheryl Bock. The process she uses is much like building a haystack, finding a needle in it and then, wearing oven mitts, threading the needle and creating a fine needlepoint design.
More ...
