Genetically Altered Mice Provide Insight Into Stuttering

September 11th, 2019
By: JobsTherapy.com Content Staff

Could genetically engineered mice help researchers identify the neurological problems associated with stuttering, a speech disorder affecting approximately 1 percent of U.S. adults? According to a new study published in the Proceedings of the National Academy of Sciences, the answer appears to be yes, Science Daily reported in August.

Researchers believe that stuttering reflects problems with the circuits in the brain that control speech, but the precise nature of these problems is unknown. However, using mice as research subjects, scientists have concluded that a loss of cells in the brain called astrocytes is associated with stuttering, according to Science Daily.

The mice had been engineered with a human gene mutation linked to stuttering. Their loss of astrocytes was most prominent in the corpus callosum, which bridges the brains’ two hemispheres. Prior imaging studies have shown that stutterers and non-stutterers have structural and functional differences in this same region of the brain, Science Daily reported.

The study was conducted by Dr. Dennis Drayna at the National Institute on Deafness and Other Communication Disorders, part of the National Institutes of Health. Collaborators included the Washington University School of Medicine in St. Louis, the NIH's National Institute of Biomedical Imaging and Bioengineering and the National Institute of Mental Health, according to Science Daily.

"By taking a genetic approach, we have been able to begin deciphering the neuropathology of stuttering, first at the molecular level by identifying genetic mutations, and now at the cellular level," Drayna told the publication.

Stutterers experience trouble enunciating certain sounds and words and are forced to pause their speech even though they know exactly what they want to say. The condition is most common in young children, and most outgrow the problem. However, for about 25 percent of children who stutter, it becomes a lifelong problem, Science Daily said.

"The identification of genetic, molecular and cellular changes that underlie stuttering has led us to understand persistent stuttering as a brain disorder," Dr. Andrew Griffith of the National Institute on Deafness and Other Communication Disorders told Science Daily. "Perhaps even more importantly, pinpointing the brain region and cells that are involved opens opportunities for novel interventions for stuttering, and possibly other speech disorders."

In the study, researchers set out to observe changes in the brain brought on by mutations in a gene called GNPTAB, which Drayna and colleagues and previously linked to stuttering through their research. The researchers created a mouse model for stuttering by engineering this human stuttering mutation into the mice. The mice with the GNPTAB mutation paused for long periods while verbally communicating, an experience similar to humans who stutter, according to Science Daily.

Since no other changes in the mice were observed, the results support prior research suggesting mice can be used as a valid animal model for studying stuttering.

When the researchers evaluated brain tissue from the mice with the mutation, they found fewer astrocytes, especially in the corpus callosum, than in the brain tissue of normal mice. With other types of brain cells, there was no difference between the two groups. Astrocytes carry out a wide range of functions in supporting nerve cells, including providing nerve cells with oxygen, nutrients and structural support, according to Science Daily.

The corpus callosum has as many as 200 million nerve fibers and allows the left and right hemispheres of the brain to communicate, which is essential for physical coordination and speech.

During subsequent experiments, the GNPTAB mutation was engineered into individual brain cell types, instead of the whole mouse, and that confirmed that the defect in vocalization was specific to astrocytes, according to Science Daily. The mice did not have long pauses in their vocalizations when the mutation was introduced into other kinds of brain cells, according to the article.

The genes associated with stuttering in recent years are involved in intracellular trafficking, in which cells transport proteins and other cellular components to the right locations within the cell. Problems with intracellular trafficking have been associated with other neurological disorders, including Lou Gehrig’s disease, or ALS, Parkinson's disease and Alzheimer's. To researchers, this indicates that certain nerve cell pathways are especially sensitive to defects in intracellular trafficking, Science Daily reported. The research does not show that stutterers have any increased risk of developing those serious disorders, however.

If subsequent research confirms that a loss of astrocytes in the brains of people with GNPTAB mutations is responsible for stuttering, new therapeutic strategies for some people with persistent stuttering could be developed, according to Science Daily.

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