Murine Surf4 is essential for early embryonic development

Autoři: Brian T. Emmer aff001;  Paul J. Lascuna aff002;  Vi T. Tang aff002;  Emilee N. Kotnik aff002;  Thomas L. Saunders aff001;  Rami Khoriaty aff001;  David Ginsburg aff001
Působiště autorů: Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan aff001;  Life Sciences Institute, University of Michigan, Ann Arbor, Michigan aff002;  Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan aff003;  Transgenic Animal Model Core Laboratory, University of Michigan, Ann Arbor, Michigan aff004;  University of Michigan Rogel Cancer Center, Ann Arbor, Michigan aff005;  Cellular and Molecular Biology Program, University of Michigan, Ann Arbor, Michigan aff006;  Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, Michigan aff007;  Department of Human Genetics, University of Michigan, Ann Arbor, Michigan aff008;  Department of Pediatrics, University of Michigan, Ann Arbor, Michigan aff009;  Howard Hughes Medical Institute, University of Michigan, Ann Arbor, Michigan aff010
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article


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.

Klíčová slova:

Alleles – Apolipoproteins – Endoplasmic reticulum – Cholesterol – Mice – Secretion – Variant genotypes – Cargo receptors


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