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Neurogenetics

, Volume 8, Issue 2, pp 71–81 | Cite as

Whole genome expression analyses of single- and double-knock-out mice implicate partially overlapping functions of alpha- and gamma-synuclein

  • Melanie Kuhn
  • Karina Haebig
  • Michael Bonin
  • Natalia Ninkina
  • Vladimir L. Buchman
  • Sven Poths
  • Olaf RiessEmail author
Original Article

Abstract

α-Synuclein has been implicated in the pathogenesis of Parkinson’s disease. The function of α-synuclein has not been deciphered yet; however, it might play a role in vesicle function, transport, or as a chaperone. α-Synuclein belongs to a family of three proteins, which includes β- and γ-synuclein. γ-Synuclein shares 60% similarity with α-synuclein. Similar to α-synuclein, a physiological function for γ-synuclein has not been defined yet, but it has been implicated in tumorgenesis and neurodegeneration. Interestingly, neither α- (SNCA−/−), γ- (SNCG−/−), nor α/γ- (SNCA_G−/−) deficient mice are present with any obvious phenotype. Using microarray analysis, we thus investigated whether deficiency of α- and γ-synuclein leads to similar compensatory mechanisms at the RNA level and whether similar transcriptional signatures are altered in the brain. Sixty-five genes were differentially expressed in all mice. SNCA−/− mice and SNCG−/− mice shared 84 differentially expressed genes, SNCA−/− and SNCA_G−/− expressed 79 genes, and SNCG−/− and SNCA_G−/− expressed 148 genes. For many of the physiological pathways such as dopamine receptor signaling (down-regulated), cellular development, nervous system function, and cell death (up-regulated), we found groups of genes that were similarly altered in SNCA−/− and SNCG−/− mice. In one of the pathways altered in both models, we found Mapk1 as the core transcript. Other gene groups, however, such as TGF-β signaling and apoptosis pathways genes were significantly up-regulated in the SNCA−/− mice but down-regulated in SNCG−/− mice. β-synuclein expression was not significantly altered in any of the models.

Keywords

Parkinson’s disease Alpha-synuclein Gamma-synuclein Knock-out animals Microarray analysis 

Notes

Acknowledgments

We would like to thank Dr. Nguyen for helpful comments on the manuscript. This work was supported by the IZKF (01KS 9602/4)/BMBF project to OR and by Welcome Trust Grants to VB.

Supplementary material

10048_2007_79_MOESM1_ESM.doc (90 kb)
Supplementary Table S1 Full names of the differentially regulated genes in SNCA−/−, SNCG−/− and SNCA_G−/− mice belonging to figure 3 (DOC 92 kb)

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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Melanie Kuhn
    • 1
  • Karina Haebig
    • 1
    • 2
  • Michael Bonin
    • 1
    • 2
  • Natalia Ninkina
    • 3
  • Vladimir L. Buchman
    • 3
  • Sven Poths
    • 1
    • 2
  • Olaf Riess
    • 1
    Email author
  1. 1.Department of Medical GeneticsUniversity of TuebingenTubingenGermany
  2. 2.The Microarray FacilityUniversity of TuebingenTubingenGermany
  3. 3.School of BiosciencesCardiff UniversityCardiffUK

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