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Gene mutation makes worms immune to alcohol

21 July 2014
Appeared in BioNews 763

Genetically mutated worms, unable to become intoxicated by alcohol, have been created by neuroscientists. The researchers say this could lead to the development of a drug to treat symptoms of alcohol withdrawal.

Scientists inserted a human gene variant into the worm C. elegans that alters 'alcohol targets' – molecules to which alcohol binds. They found that when these worms were placed in alcohol, their behaviour did not change and they were able to move around and reproduce as normal.

'This is the first example of altering a human alcohol target to prevent intoxication in an animal', said Dr Jon Pierce-Shimomura, assistant professor of neuroscience at the University of Texas at Austin, who led the study.

The modified alcohol targets disrupted a cellular process governed by the BK channel, meaning that the biological mechanisms causing drunken behaviour were not set in motion.

The BK channel is also responsible for various other functions including regulating the activity of neurons, blood vessels and the respiratory tract. But the team were able to alter the BK channel without disrupting these other functions. 'We got pretty lucky and found a way to make the channel insensitive to alcohol without affecting its normal function', said Dr Pierce-Shimomura.

When given alcohol, C. elegans displays a number of features allowing the scientists to distinguish between sobriety and inebriation. They stop laying eggs, causing a build-up within their bodies that can be counted, and they also begin to crawl slower and wriggle less.

However, C. elegans are not an ideal model for studying the different effects of alcohol dependence such as cravings or tolerance. The team are now testing the effects if this mutation in mice, to examine whether the alcohol target affects these symptoms.

'Our findings provide exciting evidence that future pharmaceuticals might aim at this portion of the alcohol target to prevent problems in alcohol abuse disorders', said Dr Pierce-Shimomura. 'However, it remains to be seen which aspects of these disorders would benefit'.

The researchers have also said a 'James Bond' drug could someday be developed, 'which would enable a spy to drink his opponent under the table, without getting drunk himself': a seemingly more glamorous purpose for the potential drug, even though the alcohol would still affect the liver and other organs.

SOURCES & REFERENCES
Conserved Single Residue in the BK Potassium Channel Required for Activation by Alcohol and Intoxication in C. elegans
Journal of Neuroscience |  16 July 2014
Genetically engineered worms that can't get drunk could lead to a 'James Bond' sobriety pill
The Independent |  16 July 2014
Mutation Stops Worms From Getting Drunk
The University of Texas at Austin (press release) |  16 July 2014
These worms could drink you under the table
Wired |  16 July 2014
The worm that can NEVER get drunk: Mutant animal created by scientists in bid to treat alcoholics
Daily Mail |  16 July 2014
Worm Study May Keep Drunks on the Wagon
Genetic Engineering and Biotechnology News |  16 July 2014
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