Date of Award
12-1-2004
Document Type
Thesis
Degree Name
M.S. in Pharmaceutical Science
First Advisor
John C. Matthews
Second Advisor
Mary L. Haasch
Third Advisor
Asok Dasmahapatra
Relational Format
dissertation/thesis
Abstract
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treated mice and monkeys have been widely used as models for the study of Parkinson’s Disease (PD). The similarities between the toxic action of MPTP in PD animal models and the occurrence of dopamine (DA) neuron degeneration in human mutant a-synuclein transgenic fruit fly (Drosophila melanogaster) suggested that the fruit fly may share the same toxic response to MPTP as primates and planaria. We have hypothesized that relative sensitivity to MPTP in the fruit fly may represent a correlate to genetic predisposition to developing PD in human. Using the MPTP survival test for selection of insensitive flies and the climbing ability test for selection of sensitive flies, we isolated the sensitive and insensitive phenotypes through 5 generations of selective breeding. We then compared the genome-wide mRNA expression in these phenotypes versus wild type (WT) flies by cDNA microarray. Our results indicated that 50 genes were up regulated and 32 genes were down regulated in the fruit flies with MPTP sensitive genetic determinants as compared with the WT flies. Twenty six genes were up regulated and no gene was down regulated in the flies with the MPTP insensitive phenotype as compared with WT flies. Some of the fruit fly genes showing altered expression that have homologs in the human genome, have been shown to exhibit similar expression alterations in PD patients and PD animal models. Genes with altered expression in either or both of the selectively bred fruit fly may prove to be important for additional attention in future PD research.
Recommended Citation
Chen, Xinyu, "Genome-wide analysis of gene expression changes in Drosophila melanogaster with variable sensitivity to MPTP" (2004). Electronic Theses and Dissertations. 3498.
https://egrove.olemiss.edu/etd/3498
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