Genetic heterogeneity versus molecular analysis of prion susceptibility in neuroblasma N2a sublines.
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.
Chasseigneaux
Stéphanie
S
EA 3621, Faculté de Pharmacie, Université Paris 5, 4 avenue de l'Observatoire, 75270 Paris cedex 06, France.
Pastore
Manuela
M
Britton-Davidian
Janice
J
Manié
Elodie
E
Stern
Marc-Henri
MH
Callebert
Jacques
J
Catalan
Josette
J
Casanova
Danielle
D
Belondrade
Maxime
M
Provansal
Monique
M
Zhang
Yonghua
Y
Bürkle
Alexander
A
Laplanche
Jean-Louis
JL
Sévenet
Nicolas
N
Lehmann
Sylvain
S
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*
D011328:Prions