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. 2022 Jul 7;53(1):54.
doi: 10.1186/s13567-022-01075-4.

Potential genetic robustness of Prnp and Sprn double knockout mouse embryos towards ShRNA-lentiviral inoculation

Andrea Rau  1   2 , Bruno Passet  3 , Johan Castille  3 , Nathalie Daniel-Carlier  3 , Alexandre Asset  3 , Jérome Lecardonnel  3 , Marco Moroldo  3 , Florence Jaffrézic  3 , Denis Laloë  3 , Katayoun Moazami-Goudarzi  3 , Jean-Luc Vilotte  3
Affiliations

Potential genetic robustness of Prnp and Sprn double knockout mouse embryos towards ShRNA-lentiviral inoculation

Andrea Rau et al. Vet Res. .

Abstract

The Shadoo and PrP prion protein family members are thought to be functionally related, but previous knockdown/knockout experiments in early mouse embryogenesis have provided seemingly contradictory results. In particular, Shadoo was found to be indispensable in the absence of PrP in knockdown analyses, but a double-knockout of the two had little phenotypic impact. We investigated this apparent discrepancy by comparing transcriptomes of WT, Prnp0/0 and Prnp0/0Sprn0/0 E6.5 mouse embryos following inoculation by Sprn- or Prnp-ShRNA lentiviral vectors. Our results suggest the possibility of genetic adaptation in Prnp0/0Sprn0/0 mice, thus providing a potential explanation for their previously observed resilience.

Keywords: Mouse; ShRNA; Shadoo; lentivirus; prion; robustness.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
Schematic representation of study design and analysis. A Transgenic lines and lentiviral inoculations. B Embryo collection. C Transcriptomic analyses. D Hallmark gene set analysis; and E differential expression analysis.
Figure 2
Figure 2
Normalized expression of Ada in WT; Prnp0/0Sprn0/0; and Prnp0/0SprnKD mice. Values are represented as dot plots for individual samples (grey points) with means (black points) and standard deviations (bars) for each experimental group.
See this image and copyright information in PMC

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