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

Kuhn, Melanie, Haebig, Karina, Bonin, Michael, Ninkina, Natalia, Buchman, Vladimir L., Poths, Sven and Riess, Olaf 2007. Whole genome expression analyses of single- and double-knock-out mice implicate partially overlapping functions of alpha- and gamma-synuclein. Neurogenetics 8 (2) , pp. 71-81. 10.1007/s10048-007-0079-z

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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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Publisher: Springer
ISSN: 1364-6745
Last Modified: 17 May 2019 21:57
URI: http://orca.cf.ac.uk/id/eprint/63279

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