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Genetic heterogeneity versus molecular analysis of prion susceptibility in neuroblasma N2a sublines

Lookup NU author(s): Yonghua Zhang, Professor Alexander Burkle

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Abstract

The neuroblastoma-derived cell line N2a is permissive to certain prion strains but resistant sublines unable to accumulate the pathological proteinase-K resistant form of the prion protein can be isolated. We compared for gene expression and phenotypes different N2a sublines that were susceptible or resistant to the 22L prion strain. Karyotypes and comparative genomic hybridization arrays revealed chromosomal imbalances but did not demonstrate a characteristic profile of genomic alterations linked to prion susceptibility. Likewise, we showed that this phenotype was not dependent on the binding of PrPres, the expression of the prion protein gene, or on its primary sequence. We completed this analysis by looking using real-time quantitative PCR at the expression of a set of genes encoding proteins linked to prion biology. None of the candidates could account by itself for the infection phenotype, nevertheless sublines had distinct transcriptional profiles. Taken together, our results do not support a role for specific genomic abnormalities and possible candidate proteins in N2a prion susceptibility. They also reveal genetic heterogeneity among the sublines and serve as a guidance for further investigation into the molecular mechanisms of prion infection. © 2008 Springer-Verlag.


Publication metadata

Author(s): Chasseigneaux S, Pastore M, Britton-Davidian J, Manie E, Stern M-H, Callebert J, Catalan J, Casanova D, Belondrade M, Provansal M, Zhang Y, Burkle AA, Laplanche J-L, Sevenet N, Lehmann S

Publication type: Article

Publication status: Published

Journal: Archives of Virology

Year: 2008

Volume: 153

Issue: 9

Pages: 1693-1702

ISSN (print): 0304-8608

ISSN (electronic): 1432-8798

Publisher: Springer Wien

URL: http://dx.doi.org/10.1007/s00705-008-0177-8

DOI: 10.1007/s00705-008-0177-8


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Funding

Funder referenceFunder name
"GIS Infections a prions''
"Carte d'Identite des Tumeurs (CIT)''
EU-PRIONSEU Commission
FOOD-CT-2004-506579EU Commission
NEUROPRIONEU Commission
QLRT-2000-01924EU Commission

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