Thursday, November 04, 1999
Asthma-free mice bred at UC
Step may lead to gene therapy for humans
BY TIM BONFIELD
The Cincinnati Enquirer
University of Cincinnati researchers have developed a genetically altered mouse that can breathe massive amounts of smog without suffering asthma attacks.
Test results from the new transgenic mice were published in today's edition of the Journal of Biological Chemistry by Drs. Stephen Liggett and Dennis McGraw, who have spent the past two years on the asthma mouse project.
The special mice, research ers say, are a key early step on a long path toward developing a genetic therapy for asthma, which affects about 15 million Americans.
In a human or mouse asthma attack, exposure to various irritants such as smog can cause the smooth muscles of the airway to constrict, thus making it hard to breathe. Many asthma medications are based on chemicals that cause those muscles to relax.
With the engineered mice, the researchers have permanently altered DNA so that the red-eyed, white-furred rodents express large amounts of the human beta-2 adrenergic receptor, which helps relax the smooth muscles of the airway instead of a medication.
Then they exposed the mice to high doses of ozone and other substances known to trigger asthma attacks in normal mice. The engineered mice breathed the harmful vapors as if nothing unusual happened.
The difference in breathing was visible to the naked eye, but the researchers also created special devices to measure the mouse breathing patterns.
“Do you know how difficult it is to measure breathing in mice? They breathe about 200 times a minute, and they only take in about (half a cubic centimeter) per breath,” Dr. Liggett said.
Much more work is needed before this genetic therapy could be used for humans.
“This was a permanent gene modification for the mice that is transferred to their pups,” Dr. Liggett said. “We probably don't want to do that for people.”
The mouse DNA change involved harvesting fertilized eggs from some female mice, injecting designer snippets of DNA, then implanting the eggs in other female mice. UC has produced about 50 of the special mice so far and plans to breed more.
Even though the researchers have observed no harmful side effects from rewriting this part of the mouse genetic code, ethical concerns may prevent similar embryo treatment in humans, Dr. Liggett said.
Instead, the researchers hope to produce a genetic medication that could be absorbed by fully developed human lungs and last three to six months between treatments.
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