UH trying University of Hawaii researchers are working with colleagues at the University of Cincinnati to try to figure out why some cloned mice are obese.
to decipher
fat clones
The mice have shown obesity
despite eating the same amount
of food as other miceBy Helen Altonn
haltonn@starbulletin.com
A team led by Ryuzo Yanagimachi, UH professor of anatomy and reproductive biology, pioneered cloning of mice in 1998.
Working with mainland colleagues, they warned last year that a normal-looking cloned animal may have hidden problems. They reported in the scientific journal Genesis that many cloned animals at birth have abnormal symptoms, such as increased body weight, overgrown placentas and respiratory problems.
One strain of mice starts out normal, then at about 10 weeks old begins getting fat despite eating the same amount of food as other mice, the scientists report in this month's issue.
Stefan Moisyadi, research coordinator at the university's Biogenesis Research Lab, said biochemical studies on the mice began there and Kellie L.K. Tamashiro, a student, continued the work at the University of Cincinnati with Randall Sakai, a psychiatry professor and former Honolulu resident, and his colleagues.
Collaborating with the UH scientists on their cloned mice, they discovered that the fat mice had increased levels of leptin (a hormone produced by fat cells) and of insulin in the blood.
However, offspring of the abnormal mice weren't fat, suggesting they aren't genetically altered and the problem may lie in the tissue culture stage, Moisyadi said.
"We can observe the fatness. We know there is something different about these mice. What else is different about them that we can't observe? That is the question....
"That is why you've got to be very careful in cloning animals. If there are such problems in mice, you can bet there will be in humans."
Also tackling the question of "Are there any normal cloned mammals?" in an accompanying article in this month's Nature Medicine was Ian Wilmut, who cloned Dolly the sheep.
He referred to the work at UH and the University of Cincinnati on obese cloned mice, pointing out, "Such perturbations in development that result from manipulating embryos are well documented in sheep and cattle."
The findings on mice provide further evidence of problems in culturing embryos and "suggest that clinicians should be cautious in the introduction of new procedures ... in human reproductive medicine," Wilmut said.
"The question 'Are there any normal cloned mammals?' as posed here can not yet be answered meaningfully because it is not possible to measure expression of all genes in every tissue."
It's important that studies of clones continue to help to understand and overcome limitations of the procedures, Wilmut added. "They are also important before large-scale use of the technology in medicine or in farm animal production."
Yanagimachi and his researchers are among those hoping to resolve cloning problems because of the possibilities of using embryonic stem cells to replace dysfunctional cells and tissue causing diseases in humans.
Authors of the Genesis article include Yanagimachi and Yukiko Yamazaki, both at the UH Biogenesis Research Lab, directed by Yanagimachi; and researchers Tamashiro and Sakai at the University of Cincinnati College of Medicine. Others are Teruhiko Wakayama and Hidenori Akutsu, formerly with "Team Yana" at UH-Manoa. Wakayama now is with Advanced Cell Technology in Massachusetts and Akutsu with Fukushima Medical University in Japan.
University of Hawaii
