November 09, 2024
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Frozen embryos a success Jackson Laboratory’s ‘cryopreservation’ gives scientists another form of mouse

BAR HARBOR – Thirty years ago the only way to maintain a “stargazer” strain of mice for posterity without allowing genetic variation was to keep a breeding colony and make sure “night visitors” didn’t sneak in from another colony.

Today, the process of freezing mice embryos, perfected at Jackson Laboratory and other institutions, has proven so successful that it’s possible to keep the stargazer, a mouse with a neurological abnormality that makes its head tilt skyward, genetically pure and available without the necessity of keeping a colony going.

The world-famous laboratory, which maintains more than 2,600 strains of mice for researchers around the world, keeps 1,300 strains only as frozen embryos. Those 1,300 are less in vogue with scientists, who request only about 200 per year, said Larry Mobraaten, a senior scientist in charge of Jackson Laboratory’s “cryopreservation” work.

But recently, more and more scientists have been asking for frozen embryos instead of live mice shipped in cardboard cubicles. The stress and possibility for exposure to pathogens during the trip makes embryo shipments preferable at a time when postal regulations are becoming ever more restrictive, Mobraaten said.

Jackson Laboratory scientists just see frozen embryos as mice in a different caging system where “they just don’t have to eat,” he said. “If things are handled carefully, they should last for centuries.”

In the last 10 years, the process has been refined at Jackson Laboratory and elsewhere to yield the best results, Mobraaten said. Every year, Jackson teaches several dozen scientists who come from around the world how to freeze and unfreeze embryos.

The mice embryos are placed in plastic vials with a “cryoprotectant” solution. The vials are put in a rack and placed in a sophisticated cooling machine that brings the temperature down slowly at first. Then it brings the temperature down quickly to 385 degrees Fahrenheit below zero.

The vials are then ready to be moved into cold storage in huge stainless steel vats connected to a vacuum-sealed plumbing system that brings liquid nitrogen in from a 3,000 gallon tank outside.

The laboratory maintains 18 tanks. Each holds 37,000 vials, with about 40 embryos per vial.

Mobraaten opened a tank recently to show the boxes of vials stored within. As the lid came up, a fog from the liquid nitrogen flowed over the sides of the circular containers. Inside, each box is numbered with big gold house numerals that can still be seen despite the frost and fog.

Warming the vials is also done on a schedule designed to have as little impact on the embryos as possible. The embryos are ultimately put in foster mothers who will give birth to the mice pups.

Initially, the laboratory stored embryos to ensure they wouldn’t be lost to science. After all, it had suffered two devastating fires, one that hit Mount Desert Island in 1947 and another at the laboratory in 1989.

Jackson Laboratory first started banking embryos in 1978. “I guess at that point we were banking on good faith,” Mobraaten said.

Last year Jackson Laboratory froze 112,000 embryos. For safekeeping, some frozen embryos are maintained at an undisclosed facility in another state.

With improvements in cryopreservation, scientists worldwide have succeeded in freezing the embryos of 22 mammalian species, Mobraaten said.

Freezing embryos is cheaper than keeping whole colonies of mice alive and genetically pure year after year. To keep one strain of mice going costs about $1,500 annually. Freezing 500 embryos or more costs about $3,000, with little cost for annual maintenance.

To bring a group of the mice back costs about $1,500. But that expense is paid for by the researcher wanting to use the mice strain.

Shipping frozen embryos, although not an advertised service of Jackson Laboratory, is likely to become more common as more and more researchers have “transgenic” facilities that allow them to use an embryo to bring mice pups to life.

Jackson Laboratory also freezes ovaries and sperm. But the process with sperm isn’t as successful as it is with embryos, Mobraaten said. Work to perfect that is under way.

Mobraaten said cryopreservation will continue to be refined and expanded. The process is a huge help with the management of the rapidly growing number of mice strains available for scientific research, he said.


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