Cloned mice are super-sized, study finds

By LEE BOWMAN

 

It's not easy being a clone. Your cells age prematurely, you're prone to develop arthritis at a young age - and you get fat.

 

A new study found that cloned mice were not only larger but also heavier than a comparison group of non-cloned mice, starting at 6 to 8 weeks of age.

 

Earlier studies had demonstrated that mouse clones were prone to be bigger than otherwise similar mice. Researchers at the University of Cincinnati, led by Randall Sakai, went further and looked at all the factors that make a creature obese. Their work, involving nine cloned mice, is being published Friday in the journal Nature Medicine.

 

They found that by measuring food intake and the physique and body fat mass, as well as levels of insulin and the weight-control hormone leptin, the "cloned mice are truly obese, and not just larger than controls," according to the study.

 

Yet when female clones were mated with normal mice, the offspring's genes did not carry the obesity trait. "So it seems that this is either a result of the cloning technique that's used or the biological events involved in the cloning process itself," Sakai said.

 

Researchers saw no difference in the animals in the earliest weeks of life, "but it's hard to measure food intake or changes in metabolism at an early age. We're going back to try and catch the exact point that the divergence in the two groups takes place," Sakai said.

 

Other studies - involving cloned pigs, sheep and cows, as well as mice - have also turned up oversized offspring, advanced aging and other health problems.

 

"This is just another example of how much we don't know about the consequences of cloning," Sakai said. "Obesity is easy to see, but there may be a lot of other dysfunctions in the process of cloning that are yet to become apparent."

 

Ian Wilmut, a pioneer of animal cloning responsible for Dolly, the first cloned sheep, observed that present methods for cloning are "error prone" to such an extent that "it is questionable whether there are any clones that are entirely normal."

 

Wilmut, of the Roslin Institute in Edinburgh, Scotland, noted in a Nature Medicine commentary that there have been similar results with other cloned mammals.

 

Scientists who study cloning believe that when the nucleus of a cell from an adult is implanted into an egg cell whose nucleus has been removed, several mechanisms must line up properly to reset the adult genetic material so it can properly develop an embryo.

 

Wilmut said it's impossible for now to measure how genes are expressed in every tissue of a cloned animal throughout its life, so only the careful tracking of the health and physical characteristics of clones can help in "overcoming the limitations of the present procedures."

 

February 28, 2002

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