Researchers have created cloned mice from freeze-dried skin cells for the first time in the world, which aims to help conservationists revive populations of endangered species.
The breakthrough paves the way for countries to store skin cells from animals as an insurance policy, as the cells can be used to create clones that increase the genetic diversity of species if they are threatened with extinction in the future.
Many declining species suffer from inbreeding, which increases the risk of birth defects, but the loss of genetic diversity can also make animals more vulnerable to other threats, such as disease, which exacerbate the pressures they face.
While scientists have used frozen cells to produce clones for conservation projects, the cells are kept in liquid nitrogen, which is expensive and risky: if there’s a power outage or the liquid nitrogen isn’t replenished regularly, the cells melt and become unusable. Freeze-dried sperm can also be used to create clones, but cannot be obtained from all animals.
“If these cells can be preserved without liquid nitrogen using freeze-drying technology, it allows genetic resources from around the world to be stored cheaply and safely,” said Prof. Teruhiko Wakayama, who led the work at Yamanashi University in Japan. . “Developing countries will be able to store their own valuable genetic resources in their own countries. Also, even in endangered species where only males survive, this technology can be used to create females to revive the species.
In the latest work, the researchers freeze-dried skin cells from mouse tails and stored them for up to nine months before trying to create clones from them. Freeze-drying processes kill the cells, but scientists have discovered they can still create early-stage cloned embryos by inserting the dead cells into mouse eggs that have had their own nuclei removed.
These early-stage mouse embryos, known as blastocysts, were used to create a pool of stem cells that underwent another round of cloning. The stem cells were inserted into mouse eggs emptied of their own nuclei, resulting in embryos that the surrogate mice carried to term. The first cloned mouse, named Dorami the melon bread-loving robot from the Doraemon Manga series, was followed by 74 more. To test whether the clones had healthy fertility, nine females and three males were bred with normal mice. All females went on to have litters.
Despite the achievement, the process is inefficient—freeze drying damages the DNA in skin cells—and the success rate for creating healthy female and male mice is only 0.2 to 5.4 percent. In some of the cells, the Y chromosome was lost, resulting in female mice being born from cells derived from male animals. “If the same treatment could be performed in endangered species where only males survive, it would be possible to create females and naturally preserve the species,” the authors wrote in Nature Communications.
The work comes as scientists prepare to breed offspring from the world’s first cloned black-footed ferret, Elizabeth Ann, in a bid to increase the species’ genetic diversity. The animal was cloned from cells deep-frozen in liquid nitrogen 35 years ago.
Dr Alena Pance, from the University of Hertfordshire, said the ability to store genetic material was “hugely important” for maintaining samples of species as well as their genetic variation. But she said it was “paramount” to show that freeze-dried cells could be stored indefinitely if they were to provide an effective long-term solution.