Human GNPTAB stuttering mutations engineered into mice cause vocalization deficits and astrocyte pathology in the corpus callosum

Stuttering is a common neurodevelopmental disorder. However, the neurological causes of this disorder are poorly understood. The disorder is highly genetic, and recent discoveries have found several genes involved in this disorder, but how these lead to the unique clinical features of stuttering has been unknown. We have shown that mice carrying human stuttering mutations display vocalization deficits that recreate the salient features of human stuttering. In these mice, we have used several different complementary techniques to identify a specific deficit in astrocytes, a type of glial cell prominent in white matter tracts, particularly in the corpus callosum of these mice. These findings suggest astrocytes as a site of the neuropathology, leading to a deficit in interhemispheric connectivity in stuttering.