Transcriptional dysregulation in a transgenic model of Parkinson disease.
Alpha-synuclein has been implicated in Parkinson disease, yet the mechanism by which alpha-synuclein causes cell injury is not understood. Using a transgenic mouse model, we evaluated the effect of alpha-synuclein overexpression on gene expression in the substantia nigra. Nigral mRNA from wild type and alpha-synuclein transgenic mice was analyzed using Affymetrix gene arrays. At 3 months, before pathological changes are apparent, we observed modest alterations in gene expression. However, nearly 200 genes were altered in expression at 9 months, when degenerative changes are more apparent. Functional genomic analysis revealed that the genes altered at 9 months were predominantly involved in gene transcription. As in human Parkinson disease, gene expression changes in the transgenic model were also modulated by gender. These data demonstrate that alterations of gene expression are widespread in this animal model, and suggest that transcriptional dysregulation may be a disease mechanism that can be targeted therapeutically.
Yacoubian
Talene A
TA
Neurology Department, Center for Neurodegeneration and Experimental Therapeutics, University of Alabama at Birmingham, Birmingham, AL 35294, USA. tyacoub@uab.edu
Cantuti-Castelvetri
Ippolita
I
Bouzou
Bérengère
B
Asteris
Georgios
G
McLean
Pamela J
PJ
Hyman
Bradley T
BT
Standaert
David G
DG
D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010300:Parkinson Disease / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics*; D051844:alpha-Synuclein / Q000096:biosynthesis / Q000235:genetics
D051844:alpha-Synuclein