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Disruption of the Sec24d Gene Results in Early Embryonic Lethality in the Mouse

Transport of newly synthesized proteins from the endoplasmic reticulum (ER) to the Golgi is mediated by the coat protein complex COPII. The inner coat of COPII is assembled from heterodimers of SEC23 and SEC24. Though mice with mutations in one of the four Sec24 paralogs, Sec24b, exhibit a neural tu...

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Autores principales: Baines, Andrea C., Adams, Elizabeth J., Zhang, Bin, Ginsburg, David
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3626607/
https://www.ncbi.nlm.nih.gov/pubmed/23596517
http://dx.doi.org/10.1371/journal.pone.0061114
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author Baines, Andrea C.
Adams, Elizabeth J.
Zhang, Bin
Ginsburg, David
author_facet Baines, Andrea C.
Adams, Elizabeth J.
Zhang, Bin
Ginsburg, David
author_sort Baines, Andrea C.
collection PubMed
description Transport of newly synthesized proteins from the endoplasmic reticulum (ER) to the Golgi is mediated by the coat protein complex COPII. The inner coat of COPII is assembled from heterodimers of SEC23 and SEC24. Though mice with mutations in one of the four Sec24 paralogs, Sec24b, exhibit a neural tube closure defect, deficiency in humans or mice has not yet been described for any of the other Sec24 paralogs. We now report characterization of mice with targeted disruption of Sec24d. Early embryonic lethality is observed in mice completely deficient in SEC24D, while a hypomorphic Sec24d allele permits survival to mid-embryogenesis. Mice haploinsufficient for Sec24d exhibit no phenotypic abnormality. A BAC transgene containing Sec24d rescues the embryonic lethality observed in Sec24d-null mice. These results demonstrate an absolute requirement for SEC24D expression in early mammalian development that is not compensated by the other three Sec24 paralogs. The early embryonic lethality resulting from loss of SEC24D in mice contrasts with the previously reported mild skeletal phenotype of SEC24D deficiency in zebrafish and restricted neural tube phenotype of SEC24B deficiency in mice. Taken together, these observations suggest that the multiple Sec24 paralogs have developed distinct functions over the course of vertebrate evolution.
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spelling pubmed-36266072013-04-17 Disruption of the Sec24d Gene Results in Early Embryonic Lethality in the Mouse Baines, Andrea C. Adams, Elizabeth J. Zhang, Bin Ginsburg, David PLoS One Research Article Transport of newly synthesized proteins from the endoplasmic reticulum (ER) to the Golgi is mediated by the coat protein complex COPII. The inner coat of COPII is assembled from heterodimers of SEC23 and SEC24. Though mice with mutations in one of the four Sec24 paralogs, Sec24b, exhibit a neural tube closure defect, deficiency in humans or mice has not yet been described for any of the other Sec24 paralogs. We now report characterization of mice with targeted disruption of Sec24d. Early embryonic lethality is observed in mice completely deficient in SEC24D, while a hypomorphic Sec24d allele permits survival to mid-embryogenesis. Mice haploinsufficient for Sec24d exhibit no phenotypic abnormality. A BAC transgene containing Sec24d rescues the embryonic lethality observed in Sec24d-null mice. These results demonstrate an absolute requirement for SEC24D expression in early mammalian development that is not compensated by the other three Sec24 paralogs. The early embryonic lethality resulting from loss of SEC24D in mice contrasts with the previously reported mild skeletal phenotype of SEC24D deficiency in zebrafish and restricted neural tube phenotype of SEC24B deficiency in mice. Taken together, these observations suggest that the multiple Sec24 paralogs have developed distinct functions over the course of vertebrate evolution. Public Library of Science 2013-04-15 /pmc/articles/PMC3626607/ /pubmed/23596517 http://dx.doi.org/10.1371/journal.pone.0061114 Text en © 2013 Baines et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Baines, Andrea C.
Adams, Elizabeth J.
Zhang, Bin
Ginsburg, David
Disruption of the Sec24d Gene Results in Early Embryonic Lethality in the Mouse
title Disruption of the Sec24d Gene Results in Early Embryonic Lethality in the Mouse
title_full Disruption of the Sec24d Gene Results in Early Embryonic Lethality in the Mouse
title_fullStr Disruption of the Sec24d Gene Results in Early Embryonic Lethality in the Mouse
title_full_unstemmed Disruption of the Sec24d Gene Results in Early Embryonic Lethality in the Mouse
title_short Disruption of the Sec24d Gene Results in Early Embryonic Lethality in the Mouse
title_sort disruption of the sec24d gene results in early embryonic lethality in the mouse
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3626607/
https://www.ncbi.nlm.nih.gov/pubmed/23596517
http://dx.doi.org/10.1371/journal.pone.0061114
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