The association between Foxp2 and language was first identified in a family in which half the members had severe speech and grammar impairments. Studies showed that all the affected family members had a mutation in the Foxp2 gene. The gene is found on a region of chromosome 7 that is linked to other disorders that affect speech, including autism and specific language impairment (a broad diagnosis used to describe communication difficulties in the absence of mental retardation, hearing loss, or emotional disorders).
In the study, the team engineered mice with either one or both disrupted copies of Foxp2 in order to examine the role of this gene in social communication. These are the first mice to be engineered with this particular genetic defect.
Disruption of Foxp2 affected the ability of infant rodents to emit ultrasonic vocalizations (USVs) when separated from their mother and littermates, according to the study leader, Joseph D. Buxbaum, PhD, Associate Professor of Psychiatry, of Neuroscience, and of Geriatrics and Adult Development at Mount Sinai.
Mice with two disrupted copies of Foxp2 had a complete absence of USVs, while mice with one disrupted gene emitted USVs at a significantly reduced rate. Mice with two disrupted copies of the gene also displayed severe motor skill impairment and premature death, while single-copy mice had more modest, but still noticeable, developmental delays.
"Our findings demonstrate that Foxp2 subsumes communication across species, and, as a result, we can legitimately use the mouse to learn about the neurobiology of human speech and articulation," says Dr. Buxbaum, whose paper was published on-line this week in the Proceedings of the National Academy of Sciences.
While Foxp2 disruption affected USVs, it did not appear to influence the structure and neural control of the vocal tract. Instead, further studies on the Foxp2 mice suggest that interference with Foxp2 affects the migration and/or the maturation of neurons in the development of the cerebellum (the part of the brain responsible for the coordination of complex voluntary muscular movement, as well as the maintenance of posture and balance).
"It has been hypothesized that speech is somehow a finer example of a motor pathway -- a more demanding, more subtle pathway, but still a motor pathway," says Dr. Buxbaum. "Our animal model provides a way of addressing this issue and, in fact, supports this hypothesis."
The Foxp2 mice may also allow researchers to investigate how this gene is related to autism. A few studies suggest that Foxp2 is an autism-susceptibility gene, although a majority view is that Foxp2 is not such a gene. However, Foxp2 is a transcription factor, something that regulates the expression of other genes. "The Foxp2 mouse can now be used to determine which genes are abnormally expressed in the cerebellum in these animals," says Dr. Buxbaum. "Those genes might be legitimate autism-susceptibility genes."
Funding to create the Foxp2 mouse model was provided in part by a pilot project grant from Cure Autism Now.