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

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Abstract Shadoo, encoded by Sprn , and PrP, encoded by Prnp , are related proteins whose biological functions are still incompletely understood. Although previous knockdown experiments have suggested the necessity of Shadoo in the absence of PrP during early mouse embryogenesis, little impact of the double-knockout of these two loci was reported. To further investigate this apparent discrepancy, we compared the transcriptome of WT, Prnp 0/0 and Prnp 0/0 , Sprn 0/0 E6.5 mouse embryos following inoculation by Sprn -ShRNA or Prnp -ShRNA lentiviral vectors at the one-cell stage. Our results highlighted a significant induction of an apoptotic pathway in Prnp 0/0 E6.5 mouse embryos inoculated with Sprn -ShRNA vectors alongside interferon and to a lesser extent inflammatory responses, confirming previous reported experiments. On the contrary, ShRNA vector inoculation in Prnp 0/0 , Sprn 0/0 embryos did not induce apoptosis and resulted in lower interferon responses. Finally, comparisons of the transcriptome of WT and Prnp 0/0 , Sprn 0/0 embryos revealed only slight differences, which may in part explain the genetic robustness observed in the latter genotype. Highlights Sprn-ShRNA lentivirus vector inoculation in Prnp knockout one-cell mouse embryos results in the induction of an apoptosis pathway at E6.5, alongside interferon and to a lesser extent inflammatory responses. Sprn- or Prnp-ShRNA lentivirus vector inoculations in Prnp / Sprn knockout one-cell mouse embryos induce lower interferon responses and no apoptotic pathway at E6.5. Although wild type and Prnp / Sprn knockout E6.5 mouse embryos are transcriptomically similar, some differences might explain this apparent resilience of the double knockout genotype.

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