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

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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.

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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.

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Authors and Affiliations

  1. Department of Medical Genetics, University of Tuebingen, Calwerstrasse 7, 72076, Tubingen, Germany

    Melanie Kuhn, Karina Haebig, Michael Bonin, Sven Poths & Olaf Riess

  2. The Microarray Facility, University of Tuebingen, 72076, Tubingen, Germany

    Karina Haebig, Michael Bonin & Sven Poths

  3. School of Biosciences, Cardiff University, Cardiff, CF10 3US, UK

    Natalia Ninkina & Vladimir L. Buchman

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  1. Melanie Kuhn
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Correspondence to Olaf Riess.

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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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Kuhn, M., Haebig, K., Bonin, M. et al. Whole genome expression analyses of single- and double-knock-out mice implicate partially overlapping functions of alpha- and gamma-synuclein. Neurogenetics 8, 71–81 (2007). https://doi.org/10.1007/s10048-007-0079-z

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