Disruption of the Sec24d Gene Results in Early Embryonic Lethality in the Mouse
Open Access
- 15 April 2013
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 8 (4), e61114
- https://doi.org/10.1371/journal.pone.0061114
Abstract
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.This publication has 38 references indexed in Scilit:
- Sec24b selectively sorts Vangl2 to regulate planar cell polarity during neural tube closureNature, 2009
- Mutations affecting the secretory COPII coat component SEC23B cause congenital dyserythropoietic anemia type IINature Genetics, 2009
- Generating transgenic mice from bacterial artificial chromosomes: transgenesis efficiency, integration and expression outcomesTransgenic Research, 2009
- Structural basis of cargo membrane protein discrimination by the human COPII coat machineryThe EMBO Journal, 2008
- Secretory COPII coat component Sec23a is essential for craniofacial chondrocyte maturationNature Genetics, 2006
- Cranio-lenticulo-sutural dysplasia is caused by a SEC23A mutation leading to abnormal endoplasmic-reticulum-to-Golgi traffickingNature Genetics, 2006
- Structure of the Sec13/31 COPII coat cageNature, 2006
- Sar1p N-Terminal Helix Initiates Membrane Curvature and Completes the Fission of a COPII VesicleCell, 2005
- A structural view of the COPII vesicle coatCurrent Opinion in Structural Biology, 2004
- Multiple Cargo Binding Sites on the COPII Subunit Sec24p Ensure Capture of Diverse Membrane Proteins into Transport VesiclesCell, 2003