title: Genetic heterogeneity versus molecular analysis of prion susceptibility in neuroblasma N2a sublines.
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.
authors.affiliation: EA 3621, Faculté de Pharmacie, Université Paris 5, 4 avenue de l'Observatoire, 75270 Paris cedex 06, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Chasseigneaux
authors.forename: Manuela
authors.initials: M
authors.lastname: Pastore
authors.forename: Janice
authors.initials: J
authors.lastname: Britton-Davidian
authors.forename: Elodie
authors.initials: E
authors.lastname: Manié
authors.forename: Marc-Henri
authors.initials: MH
authors.lastname: Stern
authors.forename: Jacques
authors.initials: J
authors.lastname: Callebert
authors.forename: Josette
authors.initials: J
authors.lastname: Catalan
authors.forename: Danielle
authors.initials: D
authors.lastname: Casanova
authors.forename: Maxime
authors.initials: M
authors.lastname: Belondrade
authors.forename: Monique
authors.initials: M
authors.lastname: Provansal
authors.forename: Yonghua
authors.initials: Y
authors.lastname: Zhang
authors.forename: Alexander
authors.initials: A
authors.lastname: Bürkle
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Laplanche
authors.forename: Nicolas
authors.initials: N
authors.lastname: Sévenet
authors.forename: Sylvain
authors.initials: S
authors.lastname: Lehmann
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004198:Disease Susceptibility; D015870:Gene Expression; D018740:Genetic Heterogeneity; D007621:Karyotyping; D051379:Mice; D009447:Neuroblastoma / Q000235:genetics* / Q000378:metabolism; D009693:Nucleic Acid Hybridization; D011328:Prions / Q000235:genetics / Q000378:metabolism*
chemical_list: D011328:Prions