Date of Submission

5-2021

Document Type

Thesis

Degree Name

Master of Science in Cellular and Molecular Biology

Department

Biology and Environmental Sciences

Advisor

Carter Takacs, Ph.D.

Committee Member

Anna Kloc, Ph.D.

Committee Member

Ellen J. Hoffman, MD, Ph.D.

Keywords

Autism, ADNP Genes, Helsmoortel-Van Der Aa syndrome, Molecular Mechanisms

MeSH

Autism Spectrum Disorder, Embryonic Development, Embryology

LCSH

Autism spectrum disorders, Embryology, Genes, Behavioral embryology, Embryology, Experimental

Abstract

Autism Spectrum Disorders (ASD) are a group of debilitating neurodevelopmental disorders, estimated to affect 1 in 54 children. Despite the identification of many autism-risk genes, the underlying mechanisms for ASD remain unclear. One of the most common forms of ASD is associated with de novo mutations in the ADNP gene (Activity-Dependent Neuroprotector Homeobox; accounting for 0.17% of ASD individuals). Termed ADNP syndrome, this disorder is characterized by intellectual disability, facial dysmorphia, and is comorbid with multiple organ system deficits. We set out to use zebrafish as a model organism to gain mechanistic insights into ADNP function. Zebrafish have the advantage of being high throughput, and have been established as a model for studying behavioral phenotypes and performing drug screenings in larvae. Zebrafish have two paralogs of adnp; adnpa and adnpb. This work characterizes the spatial and temporal expression of adnpa/b during zebrafish embryonic development, and details the establishment of a CRISPR/cas9 knockout line for adnpa/b in zebrafish. This work also presents preliminary data on CRISPR/Cas13d knockdown of adnpa and improvements in the efficiency of cas13d RNA knockdown. Future work aims to study the morphological and behavioral consequences of adnpa/b loss of function, as well as the molecular mechanisms by which adnpa/b impact zebrafish embryonic development.

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