Open AccessMurine Surf4 is essential for early embryonic development
Author(s) -
Brian T. Emmer,
Paul J. Lascuna,
Vi T Tang,
Emilee N. Kotnik,
Thomas L. Saunders,
Rami Khoriaty,
David Ginsburg
Publication year - 2020
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0227450
Subject(s) - biology , embryonic stem cell , microbiology and biotechnology , endoplasmic reticulum , gene targeting , embryogenesis , germline , gene knockdown , phenotype , ldl receptor , loss function , endocrinology , cholesterol , embryo , genetics , gene , lipoprotein
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.