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Aggregation of cloned mouse embryos improves survival rate

PHILADELPHIA -- Scientists at the University of Pennsylvania have found a novel way to boost the paltry survival rate of cloned mammals: When two genetically identical cloned mouse embryos are combined, the aggregate embryo is considerably more likely to survive to birth.

A team from Penn's School of Veterinary Medicine reports the results in the Oct. 1 issue of the European Molecular Biology Organization Journal.

"At the blastocyst stage, an early embryonic stage just prior to implantation, mouse clones typically have a much lower than normal number of cells," said corresponding author K. John McLaughlin, assistant professor of animal biology. "When we combined two clones at the four-cell stage, the embryos showed a remarkable improvement in viability, much greater than expected from the sum of their parts."

Despite the successful cloning of sheep, pigs, cats and most recently rats, mammalian cloning -- in which an ordinary cell's nucleus is transferred to an egg whose nucleus has been removed -- remains remarkably inefficient. Of every 100 cloned mice, roughly one survives to birth.

The researchers found that when the clone hybrids were transferred back into the uteri of recipient mice, the survival rate jumped to 8 percent. The researchers even produced a litter of four cloned mouse pups, in stark contrast to the typical single pup born.

Cloning requires the precise genetic reprogramming of the nucleus inserted into an enucleated egg. This nucleus must abandon its former genetic program and adopt the genetic profile of an embryonic nucleus; failure to do so dooms the embryo.

"The paper provides a new insight into reprogramming following nuclear transfer," said Davor Solter, a developmental biologist at the Max-Planck Institute of Immunobiology who was not involved in this work. "It confirms indirectly that every cloned embryo is actually different and that reprogramming is random. It seems that two embryos wh
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Contact: Steve Bradt
bradt@pobox.upenn.edu
215-573-6604
University of Pennsylvania
1-Oct-2003


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