MICE FOR MEN

Today, the laboratory offers about 3,000 strains. Individual animals in each strain are essentially all the same at the genetic levels8212;an endless stream of identical twins, except for the genes determining sex. Many have traits that mimic human ailments8212;diabetes, hypertension, osteoporosis and Alzheimer8217;s disease. Others have the tendency to develop problems such as obesity, cancer or infection when subjected to the 8220;right8221; environmental conditions.

In most cases, these traits and hundreds more arose through chance mutations in single animals. They caught the eye of a scientist, who in turn 8220;captured8221; the trait by mating the animal with its siblings, and then those offspring with one another. After 25 generations, such animals are all identical and8212;if things go as planned8212;all carry the gene or genes responsible for the trait of interest.

In recent decades, genetic technology has also allowed scientists to knock out or, in some cases, add genes to animals. Of the lab8217;s 3,000 strains, about one-third are genetically engineered. The usefulness of these animals is hard to overstate. Through much of the 20th century, scientists collected mice from around the world including places as remote as the Faroe Islands in the North Atlantic for breeding stock. The idea was to ensure genetic diversity in the mix of animals used to create inbred strains.

How successful this effort was8212;or was not8212;became clear only this summer. A paper published in July in the journal Nature Genetics analysed the DNA sequences of 15 strains of mice. Eleven were 8220;classical8221; inbred strains used in laboratories for years. Four were strains derived from animals caught in the wild more recently, including one from the sewers of Prague.

To the researchers8217; surprise, the older strains had much less genetic diversity than anyone assumed. This told mouse geneticists there were many more variations of DNA in the mouse universe that could potentially go into making new strains of the animals. 8220;Only one-quarter of the total diversity in the 15 strains is present in the classical laboratory strains,8221; said Churchill, a biostatistician at the Jackson Lab.

To that end, the Jackson Laboratory and the US Government8217;s Oak Ridge National Laboratory in Tennessee are creating about 1,000 new strains of inbred mice. The scientists are starting with a more diverse group of 8220;founders8221; than went into current lab strains. They are creating the inbred lines through the classic technique of brother-sister mating.The work will take about seven years. The result may not be better mice, but it will be more varied ones.

LAT-WP