Article thumbnail

alan shepard, A modifier of polyglutamine toxicity in Drosophila melanogaster

By Gino Intrieri

Abstract

Neurodegenerative diseases, such as Machado-Joseph Disease (MJD), are associated with a polyglutamine expansion within a host protein. Pathological development is well studied, but not completely understood. Disease is thought to be related to protein aggregate formation in the cytoplasm, which localize to the nucleus as nuclear inclusions (NIs). Others have developed a polyglutamine disease model in Drosophila eye tissue, which expresses a disease-related gene, MJDtr-Q78. The gene encodes for a protein, Q78, which leads to neuronal toxicity in eye tissues and is easily identifiable. A potential modifier, which enhances this phenotype, was found in the 64C region of Chromosome 3. Alleles that contained transposable element (TE) induced mutations within a gene in this region, alan shepard (shep), were found to enhance the phenotype. Genetic and molecular verification show that the enhancement is directly linked to the TE, which suggests shep influences the toxicity caused by the toxic protein. Genomic analyses suggest shep encodes for an RNA binding protein. A histo-immunochemical stain reveals shep does not affect aggregate or NI formation, indicating an indirect relationship with polyglutamine diseases. shep does not modify a second polyglutamine-associated disease background, 97QP. This suggests that shep influences independent of the polyglutamine expansion tract. An investigation of the biological significance of shep reveals that the gene is required for development past pupation. Together these data support the current model, which is, although polyglutamine diseases are related to an expansion of the polyglutamine tract, their disease development can be independent of each other.

Topics: Biology, Molecular|Biology, Genetics|Biology, Neurobiology
Publisher: OpenCommons@UConn
Year: 2010
OAI identifier: oai:opencommons.uconn.edu:dissertations-5203
Download PDF:
Sorry, we are unable to provide the full text but you may find it at the following location(s):
  • https://opencommons.uconn.edu/... (external link)
  • http://gateway.proquest.com/op... (external link)
  • Suggested articles


    To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.