Date of Degree
Access restricted until 07/13/2019
MS (Master of Science)
Molecular Physiology and Biophysics
Autism Spectrum Disorders (ASDs) are a diverse group of diseases that share the common features of deficits in social communication and rigid, repetitive behavior patterns. Most genetic alterations related to ASD can be broadly split into two categories – those pertaining to mTOR/PI3K signaling, and those pertaining to synaptic connections and structure. While a number of synaptic scaffolding proteins have been linked to ASD via human genetic studies and mouse models, SAP90/PSD95 associated protein 3 (SAPAP3) has not. Loss of SAPAP3 in mice, however, results in compulsive grooming behavior, which parallels one of the core features of ASD. On a molecular level, loss of SAPAP3 results in increased signaling via the group I metabotropic glutamate receptor mGluR5. As mGluR5 is known to regulate protein transcription and translation, we conducted a proteomic comparison of sapap3-/- mice relative to sapap3+/+ mice. We identified a number of differentially regulated proteins, the majority of which were upregulated in sapap3-/- mice. Of those, we chose to further investigate collapsin response mediator protein 2 (CRMP2), due to its role in regulating dendritic branching and neurogenesis. We found abnormalities in both dendritic branching and postnatal neurogenesis in sapap3-/- mice, changes which may contribute to some of their behavioral phenotypes. We also found that ultrasonic vocalization, a form of communication for mice, is altered in neonatal sapap3-/- mice. Taken together, these findings provide new direction that could lead to future therapeutics for patients with ASD, as well as an early read-out of the effectiveness of any potential treatment.
v, 50 pages
Includes bibliographical references (pages 40-50).
Copyright © 2017 Natalya S. Tesdahl
Available for download on Saturday, July 13, 2019