Baffling genetic glitch creates stuttering mice w/ human-like speech disorder

By Beth Mole

UK Film Council

Mice that can stutter like humans may seem pretty striking. But what really renders researchers speechless is the enigmatic genetic glitch that causes stuttering.

Researchers led by Terra D. Barnes of Washington University discovered that their genetically-engineered mice stutter due to DNA defects in a humdrum “housekeeping” gene. This gene codes for a protein that simply places a "routing tag" on certain enzymes that shred cellular trash. The tag ensures that the shredding enzymes end up in chambers called lysosomes, basically the cell’s garbage disposal. It’s a mundane cellular activity, yet mutations in the same process in humans have also been linked to stuttering—a bizarrely specific condition for such a general gene. And, so far, scientists have no idea why the two are linked.

Nevertheless, the engineered mice presented with similar symptoms as humans who stutter. Though mice obviously don’t talk as humans do, they emit ultrasonic and squeaky whistle-like songs that are coded with information. Researchers have already spent plenty of time studying these songs in detail. In particular, they’ve studied the “isolation calls” belted out by newborn mice when their mothers aren’t around.

Compared with normal littermates, the genetically modified mice sang fewer isolation calls, had longer pauses within their calls, and tended to get stuck on and repeat syllables—in mouse speak that’s a vocal unit characterized by the presence and size of pitch jumps. All those vocal patterns align with the jagged, broken speech of humans who stutter.
And, just like humans who stutter, the stuttering mice didn’t suffer from any other problems. Researchers put them through a battery of experiments, testing their memory, balance, strength, coordination, learning, and sociability. The mice came out generally the same as their non-stuttering littermates.
The results, published Thursday in Current Biology, back up the connection between the housekeeping gene and stuttering in humans. And despite the inexplicable connection, researchers are hopeful that the mice will shed light on what’s really going on and how to fix it in people with the condition.
“We suggest that this animal model could allow the large array of genetic and neurobiological tools that exist in mice to be applied to the study of the cellular and molecular features of stuttering and perhaps normal speech,” the authors conclude.
For now, the researchers can only speculate as to what the mutation is doing to bring about stuttering. They note that the speech disorder’s cross-over into mice makes some sense based on what scientists have seen in humans. Because mice vocalize with whistles, while humans make sounds with vibrations in their vocal chords, it may be unlikely that the cause of stuttering is at the source of sound. In fact, researchers have also found evidence that people who are deaf or hearing impaired can stutter while using sign language. This supports the suggestion that the source of the stutter lies elsewhere.
The researchers are currently planning additional experiments with the mice to better understand the source of their stutter.
Current Biology, 2015. DOI: 10.1016/j.cub.2016.02.068 (About DOIs).