Global Ablation of the Mouse Rab11a Gene Impairs Early Embryogenesis and Matrix Metalloproteinase Secretion

Background: The physiological role of Rab11a in mouse embryogenesis has not been fully studied. Results: Using a Rab11a(null) mouse allele, the transport of multiple membrane-associated and soluble cargos was analyzed in mouse blastocysts and MEFs. Conclusion: Rab11a ablation impairs mouse blastocyst development and the secretion of soluble matrix metalloproteinases. Significance:In vivo functions of Rab11a in mouse fetal development and soluble MMP secretion were uncovered. Rab11a has been conceived as a prominent regulatory component of the recycling endosome, which acts as a nexus in the endo- and exocytotic networks. The precise in vivo role of Rab11a in mouse embryonic development is unknown. We globally ablated Rab11a and examined the phenotypic and molecular outcomes in Rab11a(null) blastocysts and mouse embryonic fibroblasts. Using multiple trafficking assays and complementation analyses, we determined, among multiple important membrane-associated and soluble cargos, the critical contribution of Rab11a vesicular traffic to the secretion of multiple soluble MMPs. Rab11a(null) embryos were able to properly form normal blastocysts but died at peri-implantation stages. Our data suggest that Rab11a critically controls mouse blastocyst development and soluble matrix metalloproteinase secretion.