Stuttering is a speech disorder in which the flow of speech is disrupted by frequent repetitions, prolongations or hesitations. Scientists do not completely understand the precise reasons why some people experience stuttering, but recent research has found that among cases of persistent stuttering in the absence of other symptoms, 9–16% of cases are associated with mutations in the lysosomal enzyme-targeting pathway. This pathway is responsible for cellular 'housekeeping' and depends on the products of three particular genes; among humans who stutter, mutations have been found in all three of these genes.

Terra Barnes and peers at Washington University (St. Louis, MO) and the National Institutes of Health (Bethesda, MD) recreated this genetic condition in mice by creating a knock-in mutation in the gene Gnptab (Curr. Biol. doi:10.1016/j.cub.2016.02.068; published online 25 April 2016). This gene, when mutated, is known to cause stuttering in human speech, and the researchers hoped that a similar disruption would occur in the vocalizations of the mutant mice. To test this, they isolated pups from their mothers in order to elicit and record vocalizations known as 'isolation calls'.

These mutant mice did, indeed, produce distinctive vocalizations that, according to Barnes, “mimic some features of human stuttering.” These mice had significantly fewer vocalizations with a higher incidence of long pauses, compared to wild-type littermates. Mutants also showed signs of temporal stereotypy in their bouts of vocalizations, repeating the same syllables more often and with less diversity than their wild-type peers.

Like stuttering humans, these mice showed no obvious non-vocal abnormalities, which suggests that this model might reproduce non-syndromic stuttering as it occurs in humans, through similar changes in the lysosomal enzyme-targeting pathway. In a press release, senior author Timothy Holy suggested how this might come about: “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.”

If this murine phenotype does in fact model stuttering in humans, it could help to establish a neurophysiological basis for this condition, and Barnes, Holy and their team are already planning next steps to tease apart potential causes and mechanisms of this very specific communicative disorder.