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Date of Award

Spring 2005

Document Type

Restricted Thesis: Campus only access

Degree Name

Bachelor of Science

Department

Biology

First Advisor

Dr. John M. Warrick

Abstract

Machado-Joseph disease (MID), or spino-cerebellar ataxia 3 (SCA-3), is a genetic neurodegenerative disease caused by the mutant ataxin-3 protein, which is characterized by an expansion of a normally occurring polyglutamine domain. It is one member of a family of diseases in which a normally occurring glutamine repeat within the protein has been expanded two to three times its normal length. This late onset disease causes severe neurological dysfunction, including loss of motor control, inability to swallow and frequent urination (1). The molecular hallmark of MID is the formation of nuclear inclusion bodies, which are aggregates of mutant ataxin-3 that trap cellular components linked to the proteasome as well as chaperones and transcription factors (2).

Expression of the truncated mutant ataxin-3 protein in the eyes and brain of the fruit fly Drosophila melanogaster has been found to cause severe neurodegeneration in those organs as well as cause loss of visual function and premature death (3). With conserved degenerative gene products being expressed, homologous modifiers of the disease can be expressed too. Previous research using a truncated form of the ataxin-3 protein has shown that modulation of various molecular chaperones and endogenous chromatin modifiers can have various effects on the pathology of MID.

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