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The Prion-like protein Shadoo is involved in mouse embryonic and mammary development and differentiation. | LitMetric

AI Article Synopsis

  • Shadoo is part of the prion protein family, which is known for its role in diseases like Transmissible Spongiform Encephalopathies, but its biological functions are still not well understood.
  • Previous experiments on the Sprn gene showed mixed results, but an in-depth analysis using a specific genetic background revealed that knocking out the Sprn gene led to increased embryonic lethality, stunted growth in pups, and lactation issues in mothers.
  • The study also found that Shadoo plays significant roles in early mouse embryogenesis and tissue development, suggesting a complex relationship between Shadoo and other prion proteins like PrP.

Article Abstract

Shadoo belongs to the prion protein family, an evolutionary conserved and extensively studied family due to the implication of PrP in Transmissible Spongiform Encephalopathies. However, the biological function of these genes remains poorly understood. While Sprn-knockdown experiments suggested an involvement of Shadoo during mouse embryonic development, Sprn-knockout experiments in 129Pas/C57BL/6J or 129Pas/FVB/NCr mice did not confirm it. In the present study, we analyzed the impact of Sprn gene invalidation in a pure FVB/NJ genetic background, using a zinc finger nuclease approach. The in-depth analysis of the derived knockout transgenic mice revealed a significant increase in embryonic lethality at early post-implantation stages, a growth retardation of young Sprn-knockout pups fed by wild type mice and a lactation defect of Sprn-knockout females. Histological and transcriptional analyses of knockout E7.5 embryos, E14.5 placentas and G7.5 mammary glands revealed specific roles of the Shadoo protein in mouse early embryogenesis, tissue development and differentiation with a potential antagonist action between PrP and Shadoo. This study thus highlights the entanglement between the proteins of the prion family.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7174383PMC
http://dx.doi.org/10.1038/s41598-020-63805-yDOI Listing

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