Saturday, April 24, 2004

FUSING CHROMOSOMES PRODUCES OFFSPRING
Experiment of mice - and no men

BY ROBERT COOKE
SPECIAL CORRESPONDENT
April 22, 2004


Males may feel less useful now that Japanese researchers have created the
first mammals - mice - via virgin birth.

By forcing the chromosomes of two females to mesh inside a single egg, the
scientists found they could produce viable offspring, one of which survived
into adulthood. Papa, alas, was left out of the loop entirely.

The milestone was announced in today's issue of the journal Nature. All
offspring were female because no male Y chromosome was involved.

Led by Tomohiro Kono at the Tokyo University of Agriculture, the nine
researchers constructed hundreds of mouse eggs containing only the
chromosomes from two females. The manipulated eggs were implanted into
surrogate mothers, and from these they obtained two female mice. One matured
into an adult of normal size and weight. She was named Kaguya after a
Japanese fairy-tale character, and produced pups of her own via normal
mating.

"It is a fascinating and very credible report," said Dr. Arthur Beaudet,
chairman of molecular and human genetics at Baylor College of Medicine in
Houston. But "I don't see it as something that would have a serious
likelihood of happening naturally. And I certainly do not see it as
something that should be tried in humans."

Reproduction sans Dad is called parthenogenesis and is seen in many species,
including snakes and birds, but not in mammals. In mouse experiments,
parthenogenic embryos die by day 10 of gestation.

Kono and colleagues got around that by using two half-sets of female genes,
called haploid sets. One special haploid set contained mutations that kept
it from acting female. Its genes functioned as though they'd come from a
male. To the researchers' surprise, only two genes - H-19 and Igf-2 - were
involved in controlling the imprinting process. This mechanism is a
mysterious alternative means of gene control. Both mother and father try to
control how genes are used through imprinting, which alters what genes do
without causing genetic damage.

The imprinting process has been a biological puzzle for decades, and the
spermless births in Japan may help resolve it.

According to animal reproduction physiologist George Seidel at Colorado
State University, theoretically "there is no good reason why
[parthenogenesis] shouldn't work, apart from imprinting. It works in other
animals, from birds on down." He said it seems Kono's team has found a way
around genetic imprinting.

He said that may lead to a new way to create stem cells used to grow new
tissues for sick people, thus avoiding use of human embryos to harvest stem
cells. In any case, Seidel said, the new results "tell us something about
control of the imprinting process." That could be important because several
genetic diseases are known to result from faulty gene imprinting.

The team in Japan saw evidence that imprinting influences perhaps 1,000 or
so other genes, and "it's amazing that altering the expression of just two
imprinted genes can have a ripple effect on the rest of the genome,"
Australian scientists wrote in a commentary in the journal Nature.

David Loebel and Patrick Tam at the Children's Research Institute of the
University of Sydney added that the work provides evidence that "expression
of imprinted genes is one of the major reasons why natural parthenogenesis
has not been possible. What is not understood is why such a barrier in
single-parent reproduction has evolved."

Harvard biologist David Haig suggests it's a matter of continuing
competition between the sexes. He suggested that the father's genes and the
mother's genes compete to influence the future. For example, Dad's genes
want to make big, healthy males who are likely to pass his genes along.
Mom's genes try to steer energy into keeping her healthy, allowing her to
reproduce again, perhaps with different males, increasing chances of passing
her genes along.

In effect, it's perhaps the battle of the sexes - writ small.
Copyright © 2004, Newsday, Inc.






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