Flies carry gene for alcohol sensitivity.

Just as some human party-goers get tipsy after only a few drinks, some fruit flies carry a genetic mutation that makes them unusually wobbly when exposed to alcohol vapors.

The mutant strain of flies, fittingly dubbed cheapdate, fall out of a lab apparatus filled with ethanol fumes faster than normal flies. Identification of this alcohol-sensitivity gene, reported in the June 12 Cell, may aid efforts to find a genetic basis for alcoholism in humans (SN: 7/8/95, p. 20).

Scientists have not firmly connected a specific human gene to alcoholism or alcohol tolerance, although alcoholism shows a hereditary pattern. People with a high tolerance for alcohol are more likely to develop the disease, and scientists suspect that differences in people's tolerance for alcohol have genetic roots.

Now scientists will look for a counterpart to the mutant fly gene in mice and humans, predicts Robert Karp, a geneticist at the National Institute on Alcohol Abuse and Alcoholism in Bethesda, Md. Two previously identified human genes with similarities to the fly gene play roles in hormone production.

The flies, of the widely studied Drosophila melanogaster species, offer a largely untapped resource to identify other genes that might influence alcohol's effects in mammals, Karp and others say. The insects can be bred and tested faster and more cheaply than rodents.

"In flies, genetic technology is so powerful because you can [find] lots of mutants and analyze them quickly," Karp says. Despite the obvious differences between humans and flies, a lot is conserved at the genetic level, he adds.

Geneticist Ulrike Heberlein of the University of California, San Francisco and her colleagues isolated the alcohol-sensitive flies by using a device they call an inebriometer. They loaded flies into the top of a 4-foot glass tube lined with baffles, which resemble rungs on a ladder.

After 20 minutes of exposure to alcohol-laden air, normal flies typically lost their ability to cling to the baffles and fell from the bottom of the tube. Flies possessing the cheapdate mutation plummeted out after an average of just 15 minutes.

The gene altered by the cheapdate mutation is part of a cellular pathway that activates hormones via a molecule called cyclic AMP. Scientists had previously found that mutations in this gene cause memory and learning deficiencies in flies.

Flies with these mutations appear to manufacture below-normal amounts of cyclic AMP. When the scientists treated cheapdate flies with chemicals that increased their production of cyclic AMP, their alcohol tolerance rose to that of normal flies. The researchers do not yet understand why low cyclic AMP production increases alcohol sensitivity.