Award Date

5-1-2022

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Life Sciences

First Committee Member

Mira Han

Second Committee Member

Kathryn Rafferty

Third Committee Member

Sean Neiswenter

Fourth Committee Member

Amei Amei

Number of Pages

122

Abstract

A genetic mutation of the Tub gene encodes a nonfunctional Tubby protein that can lead to retinal degeneration, hearing loss, and late-onset obesity in the mouse. The Tubby protein is a member of tubby-like proteins, found in many organisms. Of importance to humans is a mutation on the Tulp1 gene that has been linked to retinal degeneration. The mechanisms leading to the development of these disease phenotypes are still not clear. Tubby is a predicted transcription factor that can possibly regulate other disease-associated genes. However, expression data on genes regulated by Tubby have thus far been scarce. To bridge this gap, the current study determined the genes regulated by Tubby to gain a better understanding of how a single loss-of-function mutation led to the tubby disease phenotypes, particularly retinal degeneration. RNA sequencing was performed on retinas from 3-month old tubby and wild-type mice followed by data analysis using standard bioinformatics tools. Expression levels of select target genes were experimentally validated with RT-qPCR. We observed 2,899 significant differentially expressed genes in the tubby mouse retina. 339 genes were downregulated while 783 genes were upregulated. Amongst the most upregulated genes are those involved in the pro-inflammatory response, while notable downregulated genes are those that function in phototransduction pathways and retinal development, thus highlighting the role of the Tubby protein in the retina. These findings suggest that genes involved in maintenance of retinal health and vision are regulated by and might be direct transcriptional targets of the Tubby protein.

Controlled Subject

Retina;Mice;Mutation (Biology);Retinal degeneration

Disciplines

Bioinformatics | Biology

File Format

pdf

File Size

3300 KB

Degree Grantor

University of Nevada, Las Vegas

Language

English

Rights

IN COPYRIGHT. For more information about this rights statement, please visit http://rightsstatements.org/vocab/InC/1.0/

Available for download on Tuesday, May 15, 2029


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