1. Poster Session PPo6: Functions and Cell Biology of PrP
- Author
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Manal Khalife, Jean-Luc Vilotte, Marie-Laure Martin-Magniette, Sead Chadi, Jean-Pierre Renou, Frédérique Bitton, Vincent Béringue, Hubert Laude, Lucas Lefevre, Sandrine Balzergue, Bruno Passet, Gaëlle Tilly, Sandrine Guillou, Marthe Vilotte, Fabienne Le Provost, Rachel Young, and Ludivine Soubigou-Taconnat
- Subjects
Genetically modified mouse ,0303 health sciences ,Microarray ,Embryogenesis ,Locus (genetics) ,Cell Biology ,Biology ,Biochemistry ,Embryonic stem cell ,Phenotype ,PRNP ,Cell biology ,Transcriptome ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Infectious Diseases ,030217 neurology & neurosurgery ,030304 developmental biology - Abstract
The physiological function of the PrP remains largely elusive. Its invalidation does not affect mouse survival and induces subtle phenotypes. To potentially assess this conundrum, we first comparatively analyzed the adult brain transcriptome of wild-type mice with that of transgenic mice invalidated at this locus either at the zygotic (Zurich PrP0/0 mice) or adult stages (NFH-Cre-Lox mice). Only subtle differences could be evidenced in the adult brains following microarray and QPCR analyses. When performed at an early adult stage, neuronal Prnp disruption appeared to sequentially induce an oxidative stress response and a nervous system remodeling, but it involved a limited number of only slightly modified genes. In sharp contrast, analysis at early embryonic stages, 7.5 and 8.5 dpc, just after the suspected normal time set of the Prnp locus activation, led to a transient perturbation of the transcriptome involving a larger number of genes and pointing to potential pathways related to the PrP physiological function. Overall, our data suggests an early adaptation of the mouse to the potentially detrimental lack of PrP during embryogenesis while its presence is less influential or redundant at later developmental stages.
- Published
- 2010