title: Wild-type and mutant alpha-synuclein induce a multi-component gene expression profile consistent with shared pathophysiology in different transgenic mouse models of PD.
abstract: The pathophysiological processes that cause Parkinson's disease (PD) affect dopamine neurons residing in the substantia nigra with devastating consequences for normal movement. One important gene involved in both familial and sporadic PD is alpha-synuclein. We have generated three strains of alpha-synuclein transgenic mice to study the pathologic consequences of the targeted expression of mutant or wild-type human alpha-synuclein in a model system. We have analyzed gene expression patterns in these mice using high throughput microarrays in anatomical regions implicated in disease (substantia nigra and brainstem). Our study reveals gene dosage-dependent dysregulation of several genes important for the dopaminergic phenotype in mice over-expressing wild-type human alpha-synuclein in the substantia nigra at time points preceding neuronal cell death. Analysis of mutant alpha-synuclein mice at a time point when pathology is advanced reveals several new candidate genes that may play a role in neuronal demise and/or protein accumulation.
authors.affiliation: Center for Aging and Developmental Biology, Aab Institute for Biomedical Research, Rochester, NY 14642, USA.
authors.forename: Renee M
authors.initials: RM
authors.lastname: Miller
authors.forename: Gretchen L
authors.initials: GL
authors.lastname: Kiser
authors.forename: Tamma
authors.initials: T
authors.lastname: Kaysser-Kranich
authors.forename: Cindy
authors.initials: C
authors.lastname: Casaceli
authors.forename: Emanuela
authors.initials: E
authors.lastname: Colla
authors.forename: Michael K
authors.initials: MK
authors.lastname: Lee
authors.forename: Chockalingham
authors.initials: C
authors.lastname: Palaniappan
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Federoff
mesh_terms: D000818:Animals; D001933:Brain Stem / Q000378:metabolism; D016923:Cell Death; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D018628:Gene Dosage; D015870:Gene Expression; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D009410:Nerve Degeneration / Q000235:genetics; D009474:Neurons; D020411:Oligonucleotide Array Sequence Analysis; D010300:Parkinson Disease / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology*; D015203:Reproducibility of Results; D013378:Substantia Nigra / Q000378:metabolism / Q000503:physiopathology; D051844:alpha-Synuclein / Q000235:genetics*
chemical_list: D051844:alpha-Synuclein; D004298:Dopamine