theses

Tourette Syndrome (TS) is a neurodevelopmental disorder that is relatively common among children between school age and adolescence. Characterized by involuntary verbal and motor tics, the condition can range from barely noticeable to severely affecting the quality of life of the patient and their ability to interact with the world and others around them. The purpose of this project was to elucidate a potential physiological cause of TS using a C57BL/6 mouse model engineered to express a human missense mutation identified in TS. Due to the broad and complex spectrum of phenotypes seen in TS patients, it is hypothesized that circuits in the cortical and thalamic regions of the brain, as well as the basal ganglia, are affected in the condition. The Tourette International Collaborative Genetics Consortium identified a mutation (known as R774H) that is highly likely to be associated with TS, and is present in a protein, CELSR3, known to be crucial in the prenatal development of the aforementioned neural circuits. For this thesis proposal, mice were selectively bred to express the R774H mutation and their brains were examined for any gross, macro-scale, abnormalities in the structures of interest. Collectively, the data obtained seem to indicate that R774H does not grossly impact the development of cortical-basal ganglia-thalamocortical circuit axon tracts. This suggests that mutations in CELSR3 may instead affect development at the level of synapses and/or the regulation of circuit-wide network activity.

M.S.

Includes bibliographical references.

Text

doi:10.7282/t3-0fa0-2176

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