Supermouse! The Mutant Mouse that Cannot Get Drunk

Mutant Supermouse is Key to Curing Alcohol Abuse and Addiction

Scientists are still puzzling out the molecular mechanisms involved in intoxication and withdrawal.  Because we don’t fully understand these processes, current therapies to treat alcohol-related disorders remain wholly ineffective.  Our team at The University of Texas at Austin may have discovered a way to prevent intoxication and withdrawal in humans.  We’re raising funds to develop a mutant mouse that will help unlock these molecular processes, the necessary key in development of effective addiction treatments.

Alcohol abuse is a serious problem

Drinking alcohol responsibly can be fun at social events. For a large number of people, however, alcohol alters the way that their brain works, which compels them to drink more and more. Individuals may initially consume excessive alcohol to relieve anxiety from the stresses of work and home life, or to overcome social inhibition in order to meet new people. But if left unchecked, the habit of drinking alcohol in excess leads to uncontrolled, intentional patterns of binge drinking or chronic drinking.

Individuals suffering from alcohol abuse inflict harm on themselves, their families and society through consequential medical, professional and emotional costs. Even if you are not directly affected by alcohol abuse, the indirect costs are severe. Over 1 in 10 children witness abusive patterns of drinking from adults in their home, and approximately 1 in 4 hospital beds go to patients recovering from alcohol toxicity and withdrawal. Every two minutes, someone in the U.S. is injured, if not killed, by a drunk driver. National financial costs alone are estimated at over $220 billion per year. Sadly, these statistics increase each year in part due to ineffective medical treatments.

We need better treatments

People won’t take a pill to stop drinking when they feel well; they’ll be more receptive to treatment while experiencing alcohol withdrawal.  Withdrawal symptoms can include severe anxiety, tremors and even seizures. Because patients want to avoid these symptoms, withdrawal is an ideal point to intervene in the cycle of alcohol abuse. Heavy drinkers who suddenly and significantly curtail consumption experience withdrawal because the sedative effects of alcohol are no longer suppressing normal excitatory brain activity, leading to a hyperactivity that results in anxiety and tremors.  Unfortunately, current treatments mimic the effects of alcohol:  medical practitioners treat patients with sedatives to relieve alcohol withdrawal symptoms.  Clearly the challenge is to discover an innovative and more specific way to overcome alcohol withdrawal without sedating the patient.

New discoveries point way to a new approach

Researchers in our lab recently discovered a way to prevent alcohol withdrawal symptoms in a simple animal model. This discovery comes from an unexpected source – a tiny worm! It turns out that all animals become intoxicated and experience alcohol withdrawal symptoms at the same dose of alcohol, because alcohol acts in the same way on the same molecules in the nervous system of worm, mouse and humans. Using this simple worm, we studied how alcohol binds to a target in the nervous system called the BK potassium channel. This channel suppresses the activity of the cells in the brain called neurons, as well as muscles after they are activated. Alcohol potently activates the BK channel, which has the net effect of dampening neuronal activity and may explain the sluggishness one feels when drunk. Our lab discovered that mutating one portion of the BK channel prevents alcohol activation (Davis et al., J Neurosci 2014). This finding generalizes to humans because introduction of the same mutation in the human BK channel produced the same effect. Additionally, we discovered that the mutation significantly reduces the level of alcohol withdrawal symptoms in worm, essentially “curing” alcohol withdrawal in worms!  See additional coverage of these results by UT News and The Telegraph.

Why we're excited

Because mammals, including humans and mice, have this same BK channel, it’s critical to test our discovery in a mammalian model.  We want to know if this mutation that was so effective in worms relieves symptoms of intoxication and alcohol withdrawal if introduced into a mouse. This would represent a “supermouse” that stays sober and avoids the terrible symptoms of withdrawal. Positive results would lead to drug development that specifically targets the BK channel. In the future, individuals suffering from alcohol withdrawal would wake up in the morning and reach for a BK channel drug rather than a bottle of beer. Because the mutation in BK channel prevents sedation in worms, a BK channel drug would signify a novel and truly effective, non-sedative and non-addictive, treatment for those suffering from alcohol abuse.

How you can make a big difference

Your help is needed to provide funding to generate the mutant supermouse that carries this mutation in the BK channel, to test whether the mutation relieves withdrawal symptoms as predicted.  Funding will also support additional tests in worms of specific compounds that best target the BK channels to prevent intoxication and withdrawal.  The results will help us compel pharmaceutical companies and granting agencies like the NIH to invest in effective drug treatments. With your help, we believe we can make a real difference in the lives of addicts, their loved ones, and society-at-large.  What starts here can change the world. Raise your horns against alcohol abuse and addiction!

Jon Pierce-Shimomura, Ph.D.

Associate Professor of Neuroscience

 Waggoner Center for Alcohol and Addiction Research Fellow

The University of Texas at Austin