Document Type and Release Option
Thesis (open access)
Autism Spectrum Disorder is a class of developmental disabilities characterized by a spectrum of social, communication, and behavioral impairments in affected individuals. Studies have shown these defects stem from abnormal brain development during critical periods during early development. The underlying genetic cause of these impairments is not well understood but is believed to be a combination of a complex pairing of genetic and environmental factors. One of the genetic factors that has been recognized to influence the phenotypic symptoms of ASD is the enzyme topoisomerase 3β (top3β.) Topoisomerases are responsible for the prevention of supercoiling during DNA replication. Top3β is responsible for breaking single strands to be exchanged by adjacent chromosomes and involved in DNA and RNA catalytic activities. Due to their unique RNA catalytic capabilities, further research into this specific topoisomerase has been conducted and found to promote a mediator protein complex (TDRD3) that has been previously associated with mental disorders. These hindered neural circuits could potentially contribute to the cognitive deficits in Autism. Our current research aims to better understand the specific roles of top3β in early neurological development through an in vivo study using zebrafish embryos as a vertebrate model system. To do this we created a top3β deficiency in zebrafish embryos and conducted a behavioral analysis comparing total average duration of movement, velocity, total distance travelled, and integrated visualization. Analysis of behavioral revealed a decrease in velocity and total distance travelled, as well as, a unique, repetitive spinning pattern expressed by only the top3β deficient embryos. Antibody staining of these embryos revealed defects in spinal motor nerves in the trunk with excessive branching patterns and misconnection of synapses to their target muscles. Analyzing the top3β deficient zebrafish model would help us better understand this spectrum disorder and its potential sources, as well as, potential drug screening target to discover therapies and treatments for Autism Spectrum Disorders.
Doolittle, Sydney, "The Influence of Autism Linked Gene Topoisomerase 3B (Top3B) on Neural Development in Zebrafish" (2017). Honors College Theses. 563.