Date of Completion

Spring 5-6-2012

Thesis Advisor(s)

Michael Lynes

Honors Major

Cell Biology

Disciplines

Cell Biology | Molecular Biology

Abstract

Metallothionein (MT) is a small, cysteine-rich protein with significant immunomodulatory activity. It has been shown to play a critical role in important cellular mechanisms including heavy metal detoxification, essential metal management and the inflammatory response. MT production can be induced by a number of cellular stressors and acts to lessen the harmful effects of oxidizing agents and heavy metal exposure. Previous studies have shown that the dose of the metallothionein gene present in an individual may have significant effects on the adaptive immune response, yet the mechanism behind this phenomenon remains unknown. We hypothesize that the gene dose of metallothionein will significantly affect the lympholiferative response between three mouse strains that produce different amounts of metallothionein due to genetic manipulation. Our results suggest that deviations from the normal gene dose of MT affect the speed and degree of a lymphoproliferative response; for example, MTKO produces a more robust response than either the MT-TGN or WT strains. Further investigation is needed to determine whether the hyperproliferation of the knockout (MTKO) murine strain is a result of increased oxidative stress and damage due to the lack of functional metallothionein. The means by which MTKO lymphocytes respond more robustly to proliferative stimulation may prove significant in contributing to the body of knowledge regarding the mechanisms of autoimmune disease development and it’s therapeutic management. Insight into these MT gene disparities may help lay the groundwork for future treatments and therapies.

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