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Murine Surf4 is essential for early embryonic development.

Brian T Emmer^1,2, Paul J Lascuna², Vi T Tang^2,3

¹Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan.

|January 25, 2020

Summary

The cargo receptor SURF4 is essential for embryonic development in mice. Loss of SURF4 function leads to embryonic lethality, suggesting critical roles beyond known protein secretion pathways.

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Quantitative Analysis of Protein Expression to Study Lineage Specification in Mouse Preimplantation Embryos

Quantitative Analysis of Protein Expression to Study Lineage Specification in Mouse Preimplantation Embryos

Published on: February 22, 2016

Area of Science:

Cell Biology
Genetics
Developmental Biology

Background:

Newly synthesized proteins enter the endoplasmic reticulum (ER) lumen and require cargo receptors for transport.
SURF4 (Surfactant Regulatory Protein 4) was previously identified as a cargo receptor involved in PCSK9 secretion in cell cultures.

Purpose of the Study:

To investigate the in vivo function of the cargo receptor SURF4.
To determine the physiological consequences of SURF4 deficiency in a murine model.

Main Methods:

CRISPR/Cas9 gene editing was employed to generate Surf4 knockout mice.
Phenotypic analysis was conducted on heterozygous (Surf4+/-) and homozygous (Surf4-/-) mice.

Main Results:

Surf4+/- mice showed normal development and physiology, with no significant changes in plasma PCSK9 or cholesterol levels, but had intrahepatic apolipoprotein B accumulation.
Surf4-/- mice exhibited embryonic lethality, with complete loss of offspring between embryonic days 3.5 and 9.5.

Conclusions:

SURF4 plays an essential role in early embryonic development in mice, indicated by the embryonic lethality of Surf4-/-.
The severe phenotype of Surf4 deficiency suggests undiscovered SURF4 cargoes or functions critical for embryonic viability.