Loss of VAMP5 in mice results in duplication of the ureter and insufficient expansion of the lung

Background: Vesicle‐associated membrane protein 5 (VAMP5) is a member of the SNARE protein family, which regulates the docking and fusion of membrane vesicles within cells. Previously, we reported ubiquitous expression of VAMP5 proteins in various organs except the brain and small intestine. However, the precise roles of VAMP5 in each organ remain unclear. To explore the roles of VAMP5 in vivo, we generated VAMP5 knockout (KO) mice. Results: VAMP5 KO mice showed low birth rate and low body weight. KO embryos grew normally in the uterus, and tended to die around birth. Anatomical analysis revealed that viable KO mice often exhibited duplication of the ureter, and dead KO mice showed insufficient expansion of the lung. VAMP5 was localized in the epithelial cells of the ureter and terminal bronchiole. Conclusions: VAMP5 KO mice showed a low birth rate and abnormalities of the urinary and respiratory systems. VAMP5 KO mice died around birth, possibly due to defects in vesicoureteral flow and breathing. The results presented could provide a basis for future studies to understand the roles of VAMP5 protein. Developmental Dynamics 247:754–762, 2018. © 2018 Wiley Periodicals, Inc. Key Findings Initial phenotype analysis of VAMP5 knockout mice. VAMP5 knockout mice shows low birth rate and low body weight. VAMP5 is expressed in the urothelium and airway epithelium, and VAMP5 knockout mice shows defects in kidney, ureter, and lung.