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Murine Surf4 is essential for early embryonic development

View ORCID ProfileBrian T. Emmer, Paul J. Lascuna, View ORCID ProfileEmilee N. Kotnik, View ORCID ProfileThomas L. Saunders, View ORCID ProfileRami Khoriaty, View ORCID ProfileDavid Ginsburg
doi: https://doi.org/10.1101/541995
Brian T. Emmer
1Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan
2Life Sciences Institute, University of Michigan, Ann Arbor, Michigan
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Paul J. Lascuna
2Life Sciences Institute, University of Michigan, Ann Arbor, Michigan
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Emilee N. Kotnik
2Life Sciences Institute, University of Michigan, Ann Arbor, Michigan
3Current address: Molecular Genetics and Genomics Program, Washington University in St. Louis, Missouri
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Thomas L. Saunders
1Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan
4Transgenic Animal Model Core Laboratory, University of Michigan, Ann Arbor, Michigan
6University of Michigan Rogel Cancer Center, Ann Arbor, Michigan
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Rami Khoriaty
1Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan
5Cellular and Molecular Biology Program, University of Michigan, Ann Arbor, Michigan
6University of Michigan Rogel Cancer Center, Ann Arbor, Michigan
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David Ginsburg
1Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan
2Life Sciences Institute, University of Michigan, Ann Arbor, Michigan
5Cellular and Molecular Biology Program, University of Michigan, Ann Arbor, Michigan
6University of Michigan Rogel Cancer Center, Ann Arbor, Michigan
7Department of Human Genetics, University of Michigan, Ann Arbor, Michigan
8Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, Michigan
9Howard Hughes Medical Institute, University of Michigan, Ann Arbor, Michigan
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  • For correspondence: ginsburg@umich.edu
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ABSTRACT

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. Surf4+/- mice exhibited grossly normal appearance, behavior, body weight, fecundity, and organ development and demonstrated no significant alterations in circulating plasma levels of PCSK9, apolipoprotein B, or total cholesterol. Surf4-/- mice exhibit embryonic lethality, with complete loss of all Surf4-/- offspring between embryonic days 3.5 and 9.5. Taken together with the much milder phenotypes of PCSK9 or apolipoprotein B deficiency in mice, these findings imply the existence of additional SURF4 cargoes or functions that are essential for murine early embryonic development.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted February 07, 2019.
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Murine Surf4 is essential for early embryonic development
Brian T. Emmer, Paul J. Lascuna, Emilee N. Kotnik, Thomas L. Saunders, Rami Khoriaty, David Ginsburg
bioRxiv 541995; doi: https://doi.org/10.1101/541995
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Murine Surf4 is essential for early embryonic development
Brian T. Emmer, Paul J. Lascuna, Emilee N. Kotnik, Thomas L. Saunders, Rami Khoriaty, David Ginsburg
bioRxiv 541995; doi: https://doi.org/10.1101/541995

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