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

Content Provider	Springer Nature Link
Author	Kuhn, Melanie Haebig, Karina Bonin, Michael Ninkina, Natalia Buchman, Vladimir L. Poths, Sven Riess, Olaf
Copyright Year	2007
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.
Starting Page	71
Ending Page	81
Page Count	11
File Format	PDF
ISSN	13646745
Journal	Neurogenetics
Volume Number	8
Issue Number	2
e-ISSN	13646753
Language	English
Publisher	Springer-Verlag
Publisher Date	2007-02-22
Publisher Place	Berlin, Heidelberg
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Parkinson’s disease Alpha-synuclein Gamma-synuclein Knock-out animals Microarray analysis Molecular Medicine Human Genetics Neurosciences
Content Type	Text
Resource Type	Article
Subject	Genetics Cellular and Molecular Neuroscience Genetics (clinical)

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

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