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Date of Award

Spring 2013

Document Type

Restricted Thesis: Campus only access

Degree Name

Bachelor of Science

Department

Biochemistry & Molecular Biol.

First Advisor

Dr. Krista Stenger

Abstract

Vesicular monoamine transporter-1 (VMAT-1) is a protein that is known to transport monoamines (serotonin, dopamine, norepinephrine) into intracellular storage vesicles within cells. Single nucleotide polymorphisms (SNPs) of the human VMAT-1 (hVMAT-1) gene SLC18A1 have been associated with neuropsychiatric disorders but there is limited information available on the function of these naturally occurring hVMAT-1 proteins. The SNPs include amino acid changes of a threonine to a proline at position 4, a threonine to a serine at position 98, and a threonine to an isoleucine at position 136. The following experiments have begun to investigate the effects of these mutations on the expression of the full-length hVMAT-1 isoforma protein and on their functional capabilities. Analysis of isoform-b of hVMAT-1 which contains a deletion of 32 amino acids in the central region of the protein also occurred. Results to date have demonstrated that isoform-b has no detectable transport activity while isoform-a with 136-Thr had 20-50% less transport activity than with 136-Ile. Studies have also begun to address the behavioral consequences of knocking out the VMAT-1 gene in mice. These results revealed delayed learning processes in both male and female VMAT-1 knockout mice, as well as increased corticosterone levels in young adult female mice.

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