title: Brain transcriptional stability upon prion protein-encoding gene invalidation in zygotic or adult mouse.
abstract: BACKGROUND
  The physiological function of the prion protein remains largely elusive while its key role in prion infection has been expansively documented. To potentially assess this conundrum, we performed a comparative transcriptomic analysis of the brain of wild-type mice with that of transgenic mice invalidated at this locus either at the zygotic or at the adult stages.
  
  
  RESULTS
  Only subtle transcriptomic differences resulting from the Prnp knockout could be evidenced, beside Prnp itself, in the analyzed adult brains following microarray analysis of 24 109 mouse genes and QPCR assessment of some of the putatively marginally modulated loci. When performed at the adult stage, neuronal Prnp disruption appeared to sequentially induce a response to an oxidative stress and a remodeling of the nervous system. However, these events involved only a limited number of genes, expression levels of which were only slightly modified and not always confirmed by RT-qPCR. If not, the qPCR obtained data suggested even less pronounced differences.
  
  
  CONCLUSIONS
  These results suggest that the physiological function of PrP is redundant at the adult stage or important for only a small subset of the brain cell population under classical breeding conditions. Following its early reported embryonic developmental regulation, this lack of response could also imply that PrP has a more detrimental role during mouse embryogenesis and that potential transient compensatory mechanisms have to be searched for at the time this locus becomes transcriptionally activated.
authors.affiliation: INRA, UMR1313, Génétique Animale et Biologie Intégrative, F-78350, Jouy-en-Josas, France.
authors.forename: Sead
authors.initials: S
authors.lastname: Chadi
authors.forename: Rachel
authors.initials: R
authors.lastname: Young
authors.forename: Sandrine
authors.initials: S
authors.lastname: Le Guillou
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Tilly
authors.forename: Frédérique
authors.initials: F
authors.lastname: Bitton
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Martin-Magniette
authors.forename: Ludivine
authors.initials: L
authors.lastname: Soubigou-Taconnat
authors.forename: Sandrine
authors.initials: S
authors.lastname: Balzergue
authors.forename: Marthe
authors.initials: M
authors.lastname: Vilotte
authors.forename: Coralie
authors.initials: C
authors.lastname: Peyre
authors.forename: Bruno
authors.initials: B
authors.lastname: Passet
authors.forename: Vincent
authors.initials: V
authors.lastname: Béringue
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Renou
authors.forename: Fabienne
authors.initials: F
authors.lastname: Le Provost
authors.forename: Hubert
authors.initials: H
authors.lastname: Laude
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Vilotte
mesh_terms: D000375:Aging / Q000235:genetics*; D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D055786:Gene Knockout Techniques; D020868:Gene Silencing; D056426:Genetic Loci / Q000235:genetics; D008297:Male; D051379:Mice; D009474:Neurons / Q000378:metabolism; D011328:Prions / Q000235:genetics*; D014158:Transcription, Genetic; D015053:Zygote / Q000378:metabolism*
chemical_list: D011328:Prions