Wild-type and mutant α-synuclein induce a multi-component gene expression profile consistent with shared pathophysiology in different transgenic mouse models of PD

Renee M. Miller, Gretchen L. Kiser, Tamma Kaysser-Kranich, Cindy Casaceli, Emanuela Colla, Michael K. Lee, Chockalingham Palaniappan, Howard J. Federoff

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

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 α-synuclein. We have generated three strains of α-synuclein transgenic mice to study the pathologic consequences of the targeted expression of mutant or wild-type human α-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 α-synuclein in the substantia nigra at time points preceding neuronal cell death. Analysis of mutant α-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.

Original languageEnglish (US)
Pages (from-to)421-432
Number of pages12
JournalExperimental Neurology
Volume204
Issue number1
DOIs
StatePublished - Mar 2007

Keywords

  • Dopamine
  • Gene expression
  • Microarray
  • Neurodegeneration
  • Parkinson's disease
  • Transgenic mouse
  • α-Synuclein

Fingerprint Dive into the research topics of 'Wild-type and mutant α-synuclein induce a multi-component gene expression profile consistent with shared pathophysiology in different transgenic mouse models of PD'. Together they form a unique fingerprint.

Cite this