Monday, May 31, 1999

By Ken Sakamoto, Star-Bulletin
Male mouse Fibro plays above the male
from whom he was cloned.

at UH clone 1st
male mouse

To create Fibro, cells were
taken from the tip of a male
mouse's tail, then injected
into a donor egg

By Helen Altonn


Hey, Cumulina, you have company: Fibro, the first male cloned mouse.

University of Hawaii researchers who pioneered the cloning of Cumulina, a female mouse, also created Fibro.

Why did they start with only females?

"It happened that way -- no reason," said Ryuzo Yanagimachi, UH professor of anatomy and reproductive biology. "Girl, girl, girl -- then boy."

He said Fibro, born last October, has developed normally and produced two healthy litters with a female mate.

Post-doctoral researcher Teruhiko Wakayama "did most of the hard work" on the male cloning experiment, as well as the female cloning, Yanagimachi said. In the June issue of the journal Nature Genetics, Wakayama is first author of a report on their work.


Ryuzo Yanagimachi


Teruhiko Wakayama

The two men and other members of "Team Yana" in the John A. Burns School of Medicine made international headlines last July with the first cloning of Cumulina and generations of female mice.

People asked if the so-called "Honolulu Technique" for cloning mice could be done with males, Yanagimachi said. "We knew that females, males made no difference."

In either case, the Honolulu Technique involves injecting the nucleus from a donor mouse into an egg from which genetic information is removed.

The egg is activated to begin dividing, and developing embryos are transplanted into a foster mother.

There's just a slight gender difference in the process.

Cells were taken from the tip of an adult male mouse's tail to create Fibro. The cultured tail-tip cells resemble fibroblasts -- large, flat, oval cells responsible for the formation of fibers. Hence, his name.

Cumulina and other female clones were produced from cells related to the reproductive system -- cumulus cells surrounding developing eggs within the ovaries.

'This has just begun'

Only three of 274 transplanted embryos from donor males last fall reached full term, and two died shortly after birth. Fibro was the lone survivor.

Similar problems occurred in cloning females, Yanagimachi said. "For some reason, some cloned babies can't reach full term." Some also have respiratory problems at birth, he said.

He believes these problems can be overcome, pointing out, "There is room for improvement; this has just begun."

Among many issues being studied by his team is the question of premature aging, raised by the cloned sheep Dolly.

The 3-year-old sheep's genes were copied from a 6-year-old sheep, and Scottish scientists say the older DNA in her cells shows signs of wear typical of older animals.

Mice mature sexually about two months after birth, and donor cells 3 to 4 months old were used to produce Cumulina and Fibro, Yanagimachi said.

Cumulina is about 1 years old, and Fibro, about 8 months old. The average life span for a mouse is about two years, although Yanagimachi said he isn't sure if that holds true for laboratory mice.

So far, he said, "We do not see any signs of premature aging."

However, his group is examining the telomeres of five generations of cloned mice, he said. Telomeres are tips on chromosomes that regulate a cell's life span.

Another first for UH team

The Wakayama-Yanagimachi research is significant because it shows nonreproductive cells can be used successfully to clone either sex, possibly to reproduce endangered species or transgenic animals (those with DNA transferred from another organism).

Yanagimachi said he has received many calls from people who want to clone male dogs and horses. "A male is very precious if he is the only one."

The technique also has great medical potential for combating diseases and infertility, Yanagimachi said. But he stressed, "There is a long way to go -- not tomorrow."

"Team Yana" has had a series of firsts the past year, from creating mouse clones to green mice.

Tony Perry, an assistant professor at the medical school, used a green jellyfish gene to demonstrate a "Honolulu transgenesis" method.

The group's stunning achievements and worldwide attention resulted in more university support for the research program.

Research center in the works

Yanagimachi was given five new positions and funding for a two-story, 15,000-square-foot facility to be built next to the Biomedical Sciences Building.

"It will be called 'Institute for Biogenesis Research' or something like that," he said.

He said space will be tight, with about 22 to 25 people in five research teams, so the present quarters in the Auxiliary Services Building also will be used.

Wakayama and Perry will direct two research teams, and Yanagimachi is trying to recruit three other group leaders.

"I feel like a captain with a big ship to race and not enough fuel and food for the crew," he said.

He said the university has been generous but the medical school has suffered funding cuts, and he needs money for equipment and personnel.

An endowment fund is needed to stabilize the expanding biogenesis institute, he said.

The scientists must generate their own research funds, and since Cumulina, "I have been so busy with this kind of thing -- interviewing -- I have no time to write grant proposals," Yanagimachi said.

He said competing universities offer $100,000 a year in support funding to secure top researchers, which he can't do.

"Texas tried to take my people away with big money," he said. "They stayed loyal to us."

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