title: Disruption of the Sec24d gene results in early embryonic lethality in the mouse.
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.
authors.affiliation: Johns Hopkins Bayview Internal Medicine Residency Program, The Johns Hopkins University, Baltimore, Maryland, United States of America.
authors.forename: Andrea C
authors.initials: AC
authors.lastname: Baines
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Adams
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.forename: David
authors.initials: D
authors.lastname: Ginsburg
mesh_terms: D000483:Alleles; D000818:Animals; D001483:Base Sequence; D022202:Chromosomes, Artificial, Bacterial; D033481:Chromosomes, Mammalian; D003433:Crosses, Genetic; D047108:Embryonic Development / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D023061:Gene Order; D018390:Gene Targeting; D005804:Genes, Lethal; D005838:Genotype; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018895:Microsatellite Repeats; D008969:Molecular Sequence Data; D010641:Phenotype; D033921:Vesicular Transport Proteins / Q000737:chemistry / Q000235:genetics*
chemical_list: C583838:SEC24D protein, mouse; D033921:Vesicular Transport Proteins