PLoS ONE (Jan 2020)

Murine Surf4 is essential for early embryonic development.

  • Brian T Emmer,
  • Paul J Lascuna,
  • Vi T Tang,
  • Emilee N Kotnik,
  • Thomas L Saunders,
  • Rami Khoriaty,
  • David Ginsburg

DOI
https://doi.org/10.1371/journal.pone.0227450
Journal volume & issue
Vol. 15, no. 1
p. e0227450

Abstract

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Newly synthesized proteins co-translationally inserted into the endoplasmic reticulum (ER) lumen may be recruited into anterograde transport vesicles by their association with specific cargo receptors. We recently identified a role for the cargo receptor SURF4 in facilitating the secretion of PCSK9 in cultured cells. To examine the function of SURF4 in vivo, we used CRISPR/Cas9-mediated gene editing to generate mice with germline loss-of-function mutations in Surf4. Heterozygous Surf4+/- mice exhibit grossly normal appearance, behavior, body weight, fecundity, and organ development, with no significant alterations in circulating plasma levels of PCSK9, apolipoprotein B, or total cholesterol, and a detectable accumulation of intrahepatic apoliprotein B. Homozygous Surf4-/- mice exhibit embryonic lethality, with complete loss of all Surf4-/- offspring between embryonic days 3.5 and 9.5. In contrast to the milder murine phenotypes associated with deficiency of known SURF4 cargoes, the embryonic lethality of Surf4-/- mice implies the existence of additional SURF4 cargoes or functions that are essential for murine early embryonic development.