LONDON: The closest thing to a stuttering mouse has been created by scientists who gave rodents a genetic mutation that causes the speech disorder in humans.
Mouse pups recorded in the first week of life squeaked with more pauses and displayed more repetitive, halting patterns in the noises they produced when they carried the mutation.
But the mutated mice had no other obvious language problems and squeaked out the same rich repertoire of ultrasonic syllables – defined by abrupt changes in pitch – as normal mice.
Researchers at Washington University in St Louis worked on the mice to see whether some of the characteristics of human stuttering, or stammering, can be reproduced in rodents. The research aims to help scientists unpick the biological pathways that underpin stammering, and give them a ready way to test drugs and other potential treatments.
“These mice aren’t stuttering but they show a lot of features that are similar to a human that stutters, so this is an incredibly powerful research tool,” said Terra Barnes, whose study is published in Current Biology. “This is a huge first step towards an animal model of stuttering.”
“Once you have an animal model for the condition, you can do a lot of things you can’t do with humans. We can find the neural correlates of stuttering, identify the underlying biological mechanisms, and maybe work out how to fix it,” she added.
In the past, stammering has been blamed on anxiety, stress and even bad parenting, but the primary driver for the disorder is now considered biological, with stress potentially exacerbating the condition. In 2008, scientists at Oxford University identified changes in the brain that appear to disrupt the neural pathways needed for fluent speech.
Two years later, a team led by Dennis Drayna at the National Institute on Deafness and other Communication Disorders in Maryland, found mutations in a gene called Gnptab that appeared to cause stuttering in some people. The discovery was a surprise, because the gene is only considered important for general housekeeping duties, such as digesting waste inside the bodies’ cells.
To find out whether rodents can be made to stutter, or at least display some aspects of the condition, Barnes, Drayna and other colleagues created mice that carried the Gnptab mutations. They then recorded the noises the mice made until they were eight days old. Mouse pups make spontaneous sounds when they are taken from their mothers, but also when they are in pain, meet another mouse, or want to attract a mate.
Each recording session lasted 3.5 minutes. The mutated mice produced nearly a third fewer sounds, with longer pauses between the noises they made. Within bouts of vocal activity, the mutated mice squeaked out more single syllables than their natural littermates. The pauses are similar to the hesitations that can break up the smooth flow of speech in people who stutter, while the repetition of syllables also mirrors human stammering.
While speech remains a uniquely human skill, the patterns of speech are built on simple building blocks. To speak clearly, people have to control the timing of their breath, the fine muscles in the tongue and mouth, and be able to initiate the movements. “Those kinds of things may be shared all the way from mice to people,” said Tim Holy, a senior author on the study.
The modified mice could help researchers work out how mutations in the Gnptab gene give rise to stammering and shed light on the related mystery of how the mutation, which would affect every cell in the body, leads to a condition as specific as stuttering.
Stuttering is common in young children. So-called developmental stuttering affects about one in 20 children, but in most cases, it resolves with or without treatment. The condition is more likely to persist in males, and around four times as many men stutter than women. Among adults in the UK, about one in 100 has a stammer. The Roman Emperor Claudius famously battled a stammer, as did Britain’s King George VI.
“Twin studies have long supported the view that there is a genetic element in stuttering. It also tends to run in some families: Charles Darwin stuttered, as did his Grandfather, Erasmus,” said Robin Lickley, a reader in speech and hearing sciences at Queen Margaret University in Edinburgh. “The genetic mutations probably affect the neurological processes that support speech production. So they probably conspire to create a neurological condition.”
Speech therapy can be highly effective at helping people overcome the difficulty, and some people benefit from electronic “anti-stammering” devices that give real time audible feedback on people’s speech. But the therapies do not work for everyone, said Barnes. “We’re very keen on identifying the underlying mechanisms, because eventually that can lead us to pharmaceutical interventions,” she said.
In 2010, Holy’s team revealed that male mice burst into ultrasonic song when they came across sex pheromones from potential mates. The accidental discovery assured mice entry to the exclusive club of musical beasts, whose members mostly comprise birds, dolphins and whales. Work by a separate group at Duke University in North Carolina last year built on the findings and showed that males turned to song to woo females.
Dr ALI AHMAD
Email: [email protected]
14 April 2016