Co-invalidation of Prnp and Sprn in FVB/N mice affects reproductive performances and highlight complex biological relationship between PrP and Shadoo

Biochem Biophys Res Commun. 2021 Apr 30:551:1-6. doi: 10.1016/j.bbrc.2021.03.013. Epub 2021 Mar 10.

Abstract

Shadoo and PrP belongs to the same protein family, whose biological function remains poorly understood. Previous experiments reported potential functional redundancies or antagonisms between these two proteins, depending on the tissue analysed. While knockdown experiments suggested the requirement of Shadoo in the absence of PrP during early mouse embryogenesis, knockout ones, on the contrary, highlighted little impact, if any, of the double-knockout of these two loci. In the present study, we reinvestigated the phenotype associated with the concomitant knockout of these two genes using newly produced FVB/N Sprn knockout mice. In this genetic background, the combined two genes' knockout induces intra-uterine growth retardations, likely resulting from placental failures highlighted by transcriptomic analyses that revealed potential redundant or antagonist roles of these two proteins in different developmental-related pathways. It also induced an increased perinatal-lethality and ascertained the role of these two loci in the lactation process.

Keywords: Lactation; Lethality; Mouse; Placenta; Prion; Shadoo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn / growth & development
  • Embryonic Development
  • Female
  • GPI-Linked Proteins
  • Genes, Lethal
  • Lactation / genetics
  • Lactation / physiology
  • Male
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Nerve Tissue Proteins / deficiency
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Phenotype
  • Placentation
  • Pregnancy
  • Prion Proteins / deficiency
  • Prion Proteins / genetics
  • Prion Proteins / metabolism*
  • Reproduction / genetics
  • Reproduction / physiology*
  • Transcriptome

Substances

  • GPI-Linked Proteins
  • Nerve Tissue Proteins
  • Prion Proteins
  • Prnp protein, mouse
  • Sprn protein, mouse