Grant: Doctoral Research Award: Canada Graduate Scholarships

Autism spectrum disorder (ASD) affects about one in 66 children in Canada. It is a neurodevelopmental disorder characterized by deficits in social interactions, communication, repetitive behavior, and abnormal reactivity to sensory stimulation. While most attempts to uncover the underlying causes of ASD have been centered on the brain, growing evidence suggests that sensory abnormalities play a key role in its etiology. New research shows that dysregulation of the sensory nervous system contributes to altered brain development and behavioral symptoms in several animal models of ASD. However, the prevalence of this dysregulation among the diverse genetic causes of ASD is unknown. ANKRD11 (Ankyrin Repeat Domain 11) is a risk gene for ASD as well as KBG syndrome, a rare neurodevelopmental disorder. ANKRD11 is responsible for regulating global gene expression throughout the body during tissue development and maintenance. Patients display structural brain abnormalities, intellectual disability, and altered behaviour. While Ankrd11 has been shown to regulate brain development in a mouse model of KBG syndrome, nothing is known on its role in sensory nervous system development. Using a mouse model that eliminates Ankrd11 specifically in sensory nervous system cells, I will determine how its loss affects their function and how the consequent change in sensory input alters brain development. I will use several methods including mouse behavioral testing, brain structural analysis and sensory neuron function assays to uncover both the mechanism and outcomes of sensory neuron dysregulation in KBG syndrome. My results will show how Ankrd11 ablation in sensory neurons contributes to behavioral abnormalities observed in KBG syndrome and ASD. It will establish a mouse model for pre-clinical assays aimed at testing drugs for ASD symptoms with an alternative, sensory nervous system-mediated approach.