Defense Date
2026
Document Type
Thesis
Degree Name
Master of Science
Department
Human Genetics
First Advisor
Michael F. Miles, MD, PhD
Abstract
The risk of developing Alcohol Use Disorder (AUD) is increased with the comorbidity of an anxiety disorder. The Miles laboratory identified Ninein (Nin) as a candidate gene for modulation of the ethanol anxiolytic response in BXD recombinant inbred mice. The Miles laboratory subsequently validated this modulation of ethanol anxiolysis through viral vector deletion of Nin within the central amygdala (CeA) of C57BL/6J mice. The results showed an increase in the anxiolytic-like response to ethanol in both sexes and a decrease in chronic ethanol consumption only in female mice. To determine potential mechanisms underlying Nin modulation of behavior, here we characterize downstream effects of Ninein deletion and discuss its implications on ethanol anxiolysis and consumption.
RNA-sequencing was performed on tissue from the central amygdala (CeA) of 15 Nin-floxed C57BL/6J mice, bilaterally injected with either an AAV8-hSyn-Cre-GFP or an AAV8-hSyn-GFP viral vector with the purpose of deleting Nin. After sequencing, analysis of differentially expressed genes revealed down-regulation of genes that are enriched in gene ontology groups such as synapse assembly, structure and organization. Upregulated genes showed a striking gene ontology enrichment response for groups involved in neuroinflammation. Analysis of differentially expressed exons showed a decrease in exon 2 in the deletion mice (p-value=0.004), validating the deletion. Deconvolution of bulk RNA expression data showed no differences in neuronal proportions. This study shows that Nin deletion within the CeA of C57BL/6J mice causes different functional DEG sets of down-regulated vs. up-regulated genes with decreased expression of genes associated with synaptic organization and structure. In contrast, Nin deletion caused a vigorous upregulation of genes associated with the innate immune response and neuroinflammation. Given the potential role of Ninein in microtubule function influencing synapse structure or activity, these results may suggest a complex innate immune response after Ninein deletion, and overall, highlights Ninein’s complex role in modulating ethanol anxiolysis and consumption.
Rights
© The Author
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
5-11-2026