Thursday, May 13, 1999

University of Hawaii photo
Tony Perry and Teru Wakayama, who worked on
transgenesis research at the University of Hawaii,
hope their work will lead to improvements in
human organ transplants.

UH’s green mice:
A medical promise

The researchers' work in
transgenesis could lead to
organ transplant advances

By Helen Altonn


It's not what they ate that caused some mice in a University of Hawaii lab to turn green. They were born with a "green gene" from a jellyfish.

The team that freeze-dried mouse sperm to fertilize eggs and cloned mice has developed a new method of transferring genetic information or DNA from one organism into the egg of another.

The technique, called "Honolulu transgenesis," is reported in tomorrow's edition of the journal Science.

The researchers hope the new method of transgenesis -- transferring genetic information or DNA from one animal to another -- will lead to improvements in human organ transplants, said Tony Perry, assistant professor in the John A. Burns School of Medicine.

Ryuzo Yanagimachi heads the laboratory and "Team Yana" in the Anatomy and Reproductive Biology Department.

Perry was lead scientist for the transgenesis project with UH collaborators Teruhiko Wakayama, Yanagimachi, Hidefumi Kishikawa and Tsuyoshi Kasai. They also worked with colleagues in Japan.

"We're not interested per se in making green mice," Perry said in an interview. "I just wanted to see if this would work out of pure curiosity ... and it was absolutely amazing to see these green mice. Most extraordinary.

"It turns out the new method is on a par already, even though this is just the inception, with the standard method used."

Transgenic mice have been produced for many years, mostly by injecting DNA into the pronucleus of a one-cell embryo. This works in mice but is difficult in mammals such as cows and pigs, Perry said.

He said the Honolulu technique is "more straightforward and potentially less damaging" than having to isolate pronucleus embryos in the standard method.

"And we are able to process more samples. We are using unfertilized eggs which are easier to get in general, even from larger species. With this new method, we don't need to inject in any particular part of the cell."

Perry said other groups discovered a particular jellyfish has a gene for green fluorescent protein, and a group in Japan used it to make green mice with the old transgenic method.

His group also used jellyfish to try out its new technique because they could easily see if it works, he said. They mixed the jellyfish DNA with mouse sperm, then injected it into mouse eggs. Developing embryos were transferred into a foster mother.

About one in five offspring from the new procedure contained the jellyfish DNA -- appearing fluorescent green under ultraviolet light, Perry said.

Although the researchers used jellyfish DNA, any genetic information could be mixed with sperm. "If this method works also in livestock, then that's fantastic," Perry said.

He said transgenesis is just a sideline for him -- his major interest is the molecular mechanism by which embryonic life is initiated.

However, the researchers hope the technique will be useful in medical research to enhance and save the lives of thousands of people a year who die waiting for organ donors.

"Not everybody likes it, but for me, I think it would be a fantastic choice to use xenotransplantation, which is transplantation of organs across species," Perry said.

Human genes perhaps could be inserted into pig genomes to overcome immune rejections of pig organs transplanted to humans, he said."This is one step toward that -- that we hopefully could produce pigs whose organs the human body would not see as being foreign."

Working with the UH researchers in Japan are Masaru Okabe of the Genome Information Research Center, Osaka University, and Yutaka Toyoda of the Research Center for Protozoan Molecular Immunology, Obihiro University of Agriculture and Veterinary Medicine.

Yanagimachi, Perry and Wakayama last year drew international attention to the UH with news that they had cloned more than 50 mice. Wakayama, working on nuclear transfer experiments, was the lead scientist.

Yanagimachi, working with Wakayama, used freeze-dried sperm to fertilize eggs and create live mice.

Given additional resources after those discoveries, Yanagimachi set up five research units to expand research into cloning, gene manipulation, cell differentiation, sperm and egg fertilization and infertility.

"Yana gives us an enormous amount of freedom," Perry said. "He built a great laboratory here and gives us freedom to explore our ideas."

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