A Mutation Associated with Stuttering Alters Mouse Pup Ultrasonic Vocalizations.

Area of Science:

• Neuroscience
• Genetics
• Speech Science

Background:

• Stuttering (stammering) is a speech disorder with an unknown mechanistic basis.
• Mutations in lysosomal enzyme-targeting pathways are linked to stuttering, but the specific link to speech deficits is unclear.
• Understanding the genetic and cellular basis of stuttering requires specific models.

Purpose of the Study:

• To investigate if a specific missense mutation in the Gnptab gene, associated with human stuttering, causes vocal abnormalities in mice.
• To determine if these vocal abnormalities in mice mirror characteristics of human stuttering.
• To establish a mouse model for studying the mechanistic basis of stuttering.

Main Methods:

• Generated mice with a missense mutation in the Gnptab gene.
• Compared vocalizations of mutant mouse pups with wild-type littermates using acoustic analysis.
• Assessed non-vocal behaviors in mutant mice.
• Analyzed human speech from individuals with Gnptab mutations.

Main Results:

• Mutant mice exhibited significantly fewer vocalizations per unit time and longer pauses between vocalizations.
• The temporal sequence entropy of mouse pup vocalizations was significantly reduced.
• Mutant mice showed no differences in non-vocal behaviors compared to controls.
• Human speech analysis revealed abnormalities similar to those in mouse vocalizations.

Conclusions:

• Mutations in the Gnptab gene lead to highly specific vocalization deficits in mice.
• These findings support the Gnptab mutation's role in stuttering.
• The Gnptab mouse model is a valuable tool for studying the mechanisms underlying stuttering and related speech disorders.