Date of Award
Undergraduate Honors Thesis
Bachelor of Arts in Behavioral Neuroscience
Peter W Vanderklish
Fragile X Syndrome--the most common inherited form of intellectual disability--is characterized by low IQ, impaired social interaction, hyperactivity and impulsivity, and abnormal physical traits including an elongated face and protruding ears. Nearly half of all children with Fragile X also meet diagnostic criteria for autism spectrum disorder. Fragile X is caused by a trinucleotide repeat expansion on the X chromosome, leading to silencing of the Fragile X mental retardation gene (FMR1) and thus lack of expression of Fragile X mental retardation protein (FMRP). As a key translational suppressor, FMRP is crucial for normal neural development and synaptic function. The current study investigates a group of synaptic proteins implicated in both autism and Fragile X that may be over-expressed in Fragile X glutamatergic synapses. Additionally, previous research has shown that these proteins likely participate in a common signaling cascade that functions abnormally in Fragile X. Using the FRM1 knockout (KO) mouse, the study validated that this set of proteins was up-regulated in KO mice compared to wild-type (WT) and discovered that the downstream signaling molecules in this complex of proteins are modulated by the same neurotransmitter receptor systems that lead to exaggerated long-term depression in Fragile X. Current research on this project involves conduct functional assays of the final product of this protein complex (ADP-ribosylation factor 6) utilizing synaptoneurosomes.
Digital USD Citation
Birch, Kelly and Vanderklish, Peter W. PhD, "Changes in Synaptic Protein Content and Signaling in a Mouse Model of Fragile X Syndrome" (2016). Undergraduate Honors Theses. 20.