BAR HARBOR (AP) – Winters in Maine are cold, but the chill outside the Jackson Laboratory is nothing compared to the temperature inside the lab’s tanks of liquid nitrogen.

Eight round tanks cooled to 320 degrees below zero squat in a windowless basement room. Researchers are filling the tanks with mouse embryos, at a rate of 2,000 embryos a day.

The Jackson Lab, founded in 1929, is the world’s largest supplier of mice to scientists around the world. But a growing part of the lab’s business involves frozen embryos, not live mice.

“We can preserve genetically interesting strains of mice by freezing sperm, eggs and embryos,” says Dr. Carlisle Landel, director of the lab’s cryopreservation program. “These genetic strains are really valuable scientific reagents, tools that scientists can use to further understanding. You want to make sure they don’t get lost.”

The Jackson Lab ships out more than 2 million mice each year. But it is also one place researchers can send mice, to preserve their genes in the lab’s nitrogen tanks. Freezing embryos keeps rare DNA safe from contamination or unwanted mutations. And frozen embryos have another advantage over live mice: they never need to eat.

The first frozen cells, stored in 1977, remain inside the tanks. It took researchers two decades to freeze their first million embryos but only six more years to double that. Jackson Lab scientists froze their two-millionth embryo in late December.

The acceleration in frozen embryos followed the growth of tools to create interesting strains of mice, Landel says.

Techniques developed in the 1980s let scientists use chemicals and enzymes to create mice with targeted mutations.

The Jackson Lab’s frozen embryos are like a library of rare mice. Researchers can order from about 2,400 strains, many existing only as frozen samples. They can choose from mice that develop glaucoma, heart disease or osteoporosis, among many other diseases.

Some researchers even order frozen embryos from the lab instead of living mice, Landel says, because travel can stress grown animals, which are often subject to quarantines at their destination.

The lab makes at least one embryo shipment a week, and “as people become more aware of the advantages of receiving frozen embryos, of course that demand is going to go up,” Landel predicts.

The lab combined its freezing, in vitro technologies and mail order embryo services into one unit this year, aiming to serve this emerging market.

Program manager Dr. Rob Taft grew up on an Ohio dairy farm, where cows routinely delivered calves conceived using frozen sperm. But mouse researchers are just realizing the benefits of in vitro technology, Taft says.

“We really are at the crest of the wave of an entirely new type of drug development, drugs that address the genetic component of disease,” Taft says. “The paradigm is starting to shift.”

Because of their size and complexity, adult mice will probably never be frozen and revived, Landel says. But an embryo, conceived with the same techniques used for human fertility patients, is small enough that freezing works.

“Cryopreservation implies viability at the end,” Landel said. “We don’t call a strain frozen unless we can get it back.”

Reviving a frozen strain takes a few weeks. Scientists thaw a frozen straw full of cells, and implant up to fifteen embryos in a surrogate mother mouse. Three weeks later, if all goes well, the mother gives birth to a litter of baby mice with desired characteristics.

Keeping more than 1,500 strains frozen instead of “fresh” saves the lab about $3 million each year in food, care and housing.

And researchers who freeze embryos don’t have to worry that their mice might die out.

“One of the reasons we freeze stuff away is simple security,” Landel says.

Live animals can catch diseases, stop breeding or die when a lab floods or burns – as parts of the Jackson Lab have, twice. And mouse embryos stored in liquid nitrogen, like human embryos at a fertility clinic, can stay frozen “essentially forever,” Landel says.

Dr. Susan Ackerman knows how valuable those rare strains can be. Her study of mice whose nerve cells deteriorate in middle-aged mice was done with a strain that had been frozen for more than 10 years. The mice opened up a new avenue of research into the course of Alzheimer’s disease, she said.

“If it hadn’t been stored, it wouldn’t be available for us to dissect the process of aging and oxidative stress,” said Ackerman, a scientist at the Jackson Lab. “Storing them is the only way that you can really archive these mutants for future investigators.”

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On the Net:

Jackson Laboratory www.jax.org

AP-ES-02-15-04 1231EST

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