Stuttering in mice and people tied to ‘garbage’ gene

"One of the things we find scientifically interesting about stuttering is that it is so precisely limited to speech," says Tim Holy. "It's a very clean defect in an incredibly complex task." (Credit: julsatmidnight/Flickr)

Once thought to be caused by nervousness, stress, or even bad parenting, stuttering is now recognized as primarily biological in origin, although anxiety can exacerbate the condition.

Some people who stutter have a mutation in a gene called Gnptab. To study the condition, researchers created mice with a corresponding mutation in the same gene. Then they analyzed their vocalizations for evidence of abnormalities similar to human stuttering.

[Kids who stutter can’t hear the beat]

“Speech is obviously a unique human capacity, but the patterns of speech are built out of a lot of building blocks that are much simpler,” says Tim Holy, associate professor of neuroscience at Washington University in St. Louis and the paper’s senior author.

“You have to be able to control the timing of your breath and the fine muscles in your tongue and mouth. You have to be able to initiate movement. Those kinds of things may be shared all the way from mice to people.”

Mice make complex sounds all the time, at pitches too high for the human ear to detect.

“Pups spontaneously vocalize when they are taken from their mom,” says first author Terra Barnes, a senior scientist in Holy’s lab. “Mice vocalize when they’re in pain, when they meet another mouse, or to attract a mate.”

Stuttering mouse pups

A key characteristic of stuttering is the presence of hesitations that break up the smooth flow of speech. The researchers developed an algorithm to analyze the length of pauses in the spontaneous vocalizations of 3- to 8-day-old mouse pups. They found that mice carrying the mutation exhibited longer pauses than those without it.

Researchers applied the same algorithm to recordings of people talking, some of whom stuttered and some of whom did not. The algorithm accurately distinguished people who speak fluently from people who stutter.

Further, the syllables vocalized by mice with the mutation were less random than those of mice without the mutation. In other words, similar to people who stutter, the mice with the mutation repeated the same syllables more often, Barnes says. “We found abnormalities that mimic some features of human stuttering.”

Other than in their vocalizations, the mice with the mutation were normal. Researchers put the mice through a battery of tests—to check balance, strength, coordination, movement initiation, spatial learning, memory, sociability, and more—and found no substantial differences between mice with and without the mutation. In this respect, the mice with the mutation are like people who stutter—indistinguishable from nonstutterers in all but speech.

The team published their results in the journal Current Biology.

[Why people stutter and how to treat it]

“One of the things we find scientifically interesting about stuttering is that it is so precisely limited to speech,” Holy says. “It’s a very clean defect in an incredibly complex task.”

It is not clear how the gene relates to speech. It is known to be involved in the pathway that degrades molecules inside the cell. Mutations that cause total loss of function result in serious metabolic diseases called mucolipidosis II/III, but the mutations associated with stuttering appear to preserve much of the known function of these genes.

“It’s kind of crazy that this gene that’s involved in digesting the garbage in your cells is somehow linked to something so specific as stuttering,” Holy says. “It could be that the protein has many functions and this mutation affects only one of them. Or the mutation could very mildly compromise the function of the protein, but there’s a set of cells in the brain that is exquisitely sensitive, and if you ever so slightly compromise the function in those cells you get the observable behavioral deficit.”

Now that researchers have a mouse model of stuttering, they are developing ideas to explore the disorder further. “We’re coming up with lots of studies we can do to figure this out,” says Barnes.

The National Institutes of Health, the Intellectual and Developmental Disabilities Research Center, and a National Institute on Deafness and Other Communication Disorders Intramural grant funded the work.

Source: Washington University in St. Louis