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Science researchers report 'extremely unstable' gene expression in cloned mice

Wide variety in gene expression in mice cloned from embryonic stem cells, as well as extremely unstable gene expression in the stem cells themselves, may shed light on why current cloning methods produce few live births and abnormally large survivors, says a team of researchers in the 6 July issue of the journal Science.

The study suggests that even apparently normal cloned animals may have subtle abnormalities in gene expression, say the Science authors, led by Rudolf Jaenisch at the Whitehead Institute for Biomedical Research. Many of the cloned mice in the study survived to adulthood, however, meaning that mammals may be more tolerant of this type of widespread gene dysregulation during development than previously suspected.

As experiments with several animal species have shown, the process used to create clones, called nuclear transfer, is an inefficient one. Most cloned embryos, derived from the insertion of a donor nucleus into an emptied egg, die before birth. The clones that do survive frequently have respiratory and circulatory problems, and abnormally high birth weights.

Some researchers have suggested that abnormal expression of certain genes, called imprinted genes, may be the culprit behind these large offspring, since imprinted gene regulation has been linked to fetal growth. Imprinting is a unique "epigenetic" phenomenon--a variation in gene expression that occurs without variation in the actual DNA sequence of the genes themselves. The expression of imprinted genes is dependent on which parent transmitted the genes in question. In certain cases, a gene passed on by your mother would not be expressed, for instance, while the identical gene from your father would.

The Science researchers decided to test this link between abnormal imprinted gene expression and the peculiar biology of clones. Jaenisch and colleagues examined gene expression for several imprinted genes in the placenta a
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Contact: Ginger Pinholster
gpinhols@aaas.org
202-326-6421
American Association for the Advancement of Science
5-Jul-2001


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