The Scientist: NewsBlog:
Frozen mouse cloned
Posted by Edyta Zielinska
[Entry posted at 4th November 2008 03:42 PM GMT]

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While restoring dinosaurs from preserved mosquitoes remains as scientifically implausible as it was when the hit science fiction film Jurassic Park was made in 1993, the possibility of cloning the woolly mammoth and other extinct species just became a little bit more real. In this week's PNAS, researchers report "resurrecting" a mouse frozen for 16 years via nuclear cell transfer. "It is a major breakthrough" said Pasqualino Loi a biomedical researcher from Teramo University in Italy, who was not involved in the study. "There is hot debate on going," wrote Loi in an Email, "on the possibility to 'restore' extinct mammals, with the [woolly] mammoth in pole position." "If you had asked me five years ago" whether such a feat were possible, said Peter Mombaerts a molecular neurogeneticist Max Planck Institute of Biophysics in Frankfurt, who was not involved in the study, "I would have said 'no way.'" Standard nuclear cell transfer involves taking a live nucleus from a donor cell and implanting it into an oocyte. Ice crystals that form upon freezing, however, kill the cells unless they are treated with a cryoprotectants. In this study, Teruhiko Wakayama at RIKEN's Center for Developmental Biology in Kobe, Japan and colleagues bypassed the need for intact cells by isolating only the nuclei of cells taken from the brain, tail blood, liver, heart and other tissues taken from a thawed mouse that had been frozen for 16 years. They transferred the nuclei into mouse oocytes from which the nuclei had been removed, using a slightly modified nuclear transfer technique. Donor nuclei from the brain provided the best success rate, the researchers found. That was surprising, said Mombaerts, since "few successes have been reported with [cloning using] neuronal cells." The researchers speculated that the high glucose content in the brain might act as a cryoprotectant, shielding cells from damage. Once the researchers had established nuclear transfer embryonic stem (ntES) cell lines, they performed a second round of nuclear transfer into oocytes and implanted them into surrogate mothers which were brought to term. Four cloned mice were born from the 16 year-old frozen mouse, as well as clones of another strain of mouse that was frozen for one week. Previously, others had tried similar techniques. For example Mombaerts' group was able to generate a cloned mouse from isolated cells that had been frozen by inserting the entire thawed cell into an oocyte. But so far, no one had produced viable offspring from the dead cells of a thawed intact body. Aside from resurrecting the woolly mammoth or spurring plans to create a frozen Noah's Arc of species on the brink of extinction, the study has more immediate practical applications. Mombaerts, who, like many mouse researchers, keeps frozen "tail-tips" of mice he's cloned, said this technique could enable him to bring back "particularly precious" mouse strains for research. Ultimately, it could also make whole genome sequencing of frozen or extinct species possible by allowing researchers to multiply entire genomes within ntES cell lines prior to sequencing, though Mombaerts cautions this application will "not work in the near future." Wakayama, for one, couldn't help reaching for the more fantastical implications, however. He enjoyed the movie Jurassic Park, he said, and he would be pleased to see someone try cloning dinosaurs using his technique. Loi, however, noted that times have changed -- it might be possible to bring back the wooly mammoth, he speculated, but would it be wise to do so "in a global warming scenario?"