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New study shows normal-looking clones may be abnormal

Scientists have found the first evidence to show that even seemingly normal-looking clones may harbor serious abnormalities affecting gene expression that may not manifest themselves as outward characteristics. The findings, reported in the July 6 issue of Science by researchers at the Whitehead Institute for Biomedical Research and University of Hawaii, confirm the previous suspicion that reproductive cloning is not only inefficient, but may actually be unsafe.

In the study, scientists from Rudolf Jaenisch's laboratory and Ryuzo Yanagimachi's laboratory sought to examine the mechanisms underlying poor survival and gross overgrowth in cloned animals. They made mouse clones from embryonic stem (ES) cells and monitored the activity of imprinted genesdevelopmental genes that are controlled by special tags that do not affect the base sequence itself. They looked to see if these tags were faithfully reproduced in cloned mice and in the donor cells used to make the clones. This would tell them if the problems with cloning resulted from aberrations in donor cells or as a result of the cloning procedure itself.

Scientists found to their surprise that much of the problem lay in the make up of the donor ES cells, which they found to be extremely unstable in culture. As they divide in culture, these cells lose the tags that tell an imprinted gene to be either turned on or off during development. The researchers found that even clones made from sister stem cells had differences in their gene expression. Despite this instability, many embryos survived to adulthood, suggesting that mammalian development is surprisingly tolerant to aberrant gene regulation. "This suggests that even apparently normal clones may have subtle aberrations of gene expression that are not easily detected in the cloned animal," says Jaenisch.

The cloning procedure involves removing the nucleus, or the genetic command center, of an egg and replacing it with the nucle
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Contact: Nadia Halim
halim@wi.mit.edu
617-258-9183
Whitehead Institute for Biomedical Research
5-Jul-2001


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