Scientists track down the root of cloning problems

May 09, 2001

Despite technological advances, two major problems continue to plague the field of animal cloning: few clones survive to term and those that do are grotesquely large. The root of these problems has remained a mystery until now.

But a new study led by the Whitehead Institute traces their origin to two separate sources, reporting that while poor survival rate is influenced by the genetic background of the donor cell, the gross overgrowth of clones results from the actual procedure of cloning.

The findings will add to the crucial body of knowledge needed to improve cloning efficiency and to understand why so few clones survive to term and become healthy adults.

These findings , from Rudolf Jaenisch's lab at the Whitehead Institute of Biomedical Research, were reported on the web May 1, 2001 in the Proceedings of the National Academies of Science.

"These results are important because they identify two distinct problems that we researchers need to focus on as we work on solving the problems plaguing cloning technology. Now researchers can treat as two separate issues factors in the cloning procedure that cause enlarged animals and the factors in the genetic makeup of donor cells that influence clone survival," says Kevin Eggan, first author on the paper and a graduate student in the Jaenisch lab.

Cloning has captured the attention of biologists because of its potential benefits--the creation of cells and tissues to replace diseased ones, recovery of extinct species, creation of animal models mimicking human diseases, and generation of herds of superior agricultural animals. The cloning procedure involves removing the nucleus, or the genetic command center, of an egg and replacing it with the nucleus of an adult cell. The egg resets the developmental clock of the adult cell back to its embryonic state and gives rise to a new organism that is genetically identical to the donor adult. In practice, however, the theoretically simple procedure has proved troublesome.

Cloned animals and the placenta that nourish them before birth often are dramatically larger than their normal counterparts. Animals also frequently suffer from birth defects and die within hours of birth. These problems, collectively termed large offspring syndrome, result in only 1-5 percent of cloned animals surviving to adulthood. The reasons for these complications have remained a mystery and raised considerable concerns about the cloning process.

The Jaenisch lab found that the genetic background of the donated nucleus influences clone survival, independent of the cloning procedure. When the researchers studied clones created from inbred mice compared to outbred mice, only the clones from outbred mice survived to adulthood. "There may be specific 'survival' genes in cells from outbred mice, which protect against the detrimental effects of the manipulations involved in cloning. The race is on to identify those genes," says Eggan.

The Jaenisch lab also tested whether the actual mechanical process of removing a nucleus from a cell and then transplanting it into an egg somehow causes problems for developing clones. To test this, the researchers used embryonic stem cells, which are unique in that they can give rise to an entire organism without using the nuclear transfer cloning procedure. The researchers found that animals developing from mouse embryonic stem cells were not overgrown at birth, but embryonic stem cells used in the cloning procedure gave rise to overgrown animals.

These findings could shed light on similar phenomena observed in cloning other animals, such as cattle, sheep, pigs, and goats, says Eggan.
For more information call
Seema Kumar or Nadia Halim
at 617-258-7270

Whitehead Institute for Biomedical Research

Related Embryonic Stem Cells Articles from Brightsurf:

New mechanisms that regulate pluripotency in embryonic stem cells are discovered
A study by researchers at the Center for Cell-Based Therapy, which is supported by FAPESP, identified microRNAs involved in pluripotency maintenance and cell differentiation.

Embryonic mammary gland stem cells identified
Research team led by Prof. C├ędric Blanpain identified the mechanisms that regulate mammary gland development.

New insights into mechanisms regulating gene expression in embryonic stem cells
Researchers from Turku, Finland, have discovered new information about the mechanisms which maintain gene activity in human embryonic stem cells.

New tools to study the origin of embryonic stem cells
Researchers at Karolinska Institutet have identified cell surface markers specific for the very earliest stem cells in the human embryo.

Scientists approve the similarity between reprogrammed and embryonic stem cells
Researchers from the Vavilov Institute of General Genetics, Research Institute of Physical Chemical Medicine and Moscow Institute of Physics and Technology (MIPT) have concluded that reprogramming does not create differences between reprogrammed and embryonic stem cells.

Drug makes stem cells become 'embryonic' again
If you want to harness the full power of stem cells, all you might need is an eraser -- in the form of a drug that can erase the tiny labels that tell cells where to start reading their DNA.

Oncogene controls stem cells in early embryonic development
Many animal species delay the development of their embryos to ensure that their offspring is born at a favorable time.

Are embryonic stem cells and artificial stem cells equivalent?
Harvard Stem Cell Institute (HSCI) researchers at Massachusetts General Hospital and Harvard Medical School have found new evidence suggesting some human induced pluripotent stem cells are the 'functional equivalent' of human embryonic stem cells, a finding that may begin to settle a long running argument.

UCSF researchers control embryonic stem cells with light
UCSF researchers have for the first time developed a method to precisely control embryonic stem cell differentiation with beams of light, enabling them to be transformed into neurons in response to a precise external cue.

Protein plays unexpected role in embryonic stem cells
A protein long believed to only guard the nucleus also regulates gene expression and stem cell development.

Read More: Embryonic Stem Cells News and Embryonic Stem Cells Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to