Brain transcriptional stability upon prion protein-encoding gene invalidation in zygotic or adult mouse

Sead Chadi, Rachel Young, Sandrine Le Guillou, Gaëlle Tilly, Frédérique Bitton, Marie-Laure Martin-Magniette, Ludivine Soubigou-Taconnat, Sandrine Balzergue, Marthe Vilotte, Coralie Peyre, Bruno Passet, Vincent Béringue, Jean-Pierre Renou, Fabienne Le Provost, Hubert Laude, Jean-Luc Vilotte

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)448
JournalBMC Genomics
Volume11
Early online date22 Jul 2010
DOIs
Publication statusE-pub ahead of print - 22 Jul 2010
Externally publishedYes

Keywords

  • Aging
  • Animals
  • Brain
  • Female
  • Gene Expression Profiling
  • Gene Knockout Techniques
  • Gene Silencing
  • Genetic Loci
  • Male
  • Mice
  • Neurons
  • Prions
  • Transcription, Genetic
  • Zygote

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