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

Autor: Yonghua Zhang, Maxime Belondrade, Jacques Callebert, Josette Catalan, Janice Britton-Davidian, Nicolas Sévenet, Monique Provansal, Jean-Louis Laplanche, Stéphanie Chasseigneaux, Marc-Henri Stern, Danielle Casanova, Alexander Bürkle, Elodie Manié, Sylvain Lehmann, Manuela Pastore
Přispěvatelé: Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut des Sciences de l'Evolution de Montpellier (UMR ISEM), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre National de la Recherche Scientifique (CNRS)-Institut de recherche pour le développement [IRD] : UR226
Rok vydání: 2008
Předmět:
Zdroj: Archives of Virology
Archives of Virology, Springer Verlag, 2008, 153 (9), pp.163-1702. ⟨10.1007/s00705-008-0177-8⟩
ISSN: 0304-8608
1432-8798
DOI: 10.1007/s00705-008-0177-8⟩
Popis: 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.
Databáze: OpenAIRE