title: Neonatal Respiratory Failure with Retarded Perinatal Lung Maturation in Mice Caused by Reticulocalbin 3 Disruption.
abstract: Reticulocalbin 3 (Rcn3) is an endoplasmic reticulum lumen protein localized to the secretory pathway. As a Ca2t-binding protein of 45 kDa (Cab45)/Rcn/ER Ca2t-binding protein of 55 kDa (ERC45)/calumenin (CREC) family member, Rcn3 is reported to function as a chaperone protein involved in protein synthesis and secretion; however, the biological role of Rcn3 is largely unknown. The results presented here, for the first time, depict an indispensable physiological role of Rcn3 in perinatal lung maturation by using an Rcn3 gene knockout mouse model. These mutant mice die immediately at birth owing to atelectasis-induced neonatal respiratory distress, although these embryos are produced with grossly normal development. This respiratory distress results from a failure of functional maturation of alveolar epithelial type II cells during alveogenesis. This immaturity of type II cells is associated with a dramatic reduction in surfactant protein A and D, a disruption in surfactant phospholipid homeostasis, and a disorder in lamellar body. In vitro studies further show that Rcn3 deficiency blunts the secretion of surfactant proteins and phospholipids from lung epithelial cells, suggesting a decrease in availability of surfactants for their surface activity. Collectively, these observations indicate an essential role of Rcn3 in perinatal lung maturation and neonatal respiratory adaptation as well as shed additional light on the mechanism of neonatal respiratory distress syndrome development.
authors.affiliation: 1 State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Jiawei
authors.initials: J
authors.lastname: Jin
authors.affiliation: 1 State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Yongchao
authors.initials: Y
authors.lastname: Li
authors.affiliation: 1 State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Jiangong
authors.initials: J
authors.lastname: Ren
authors.affiliation: 1 State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Sin
authors.initials: S
authors.lastname: Man Lam
authors.affiliation: 1 State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Yidi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: 2 Department of Pulmonary Medicine, Beijing Shijitan Hospital, Capital Medical University, Beijing, China; and.
authors.forename: Yu
authors.initials: Y
authors.lastname: Hou
authors.affiliation: 1 State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: 3 Institute of Development Biology and Molecular Medicine, Fudan University, Shanghai, China.
authors.forename: Rener
authors.initials: R
authors.lastname: Xu
authors.affiliation: 1 State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Guanghou
authors.initials: G
authors.lastname: Shui
authors.affiliation: 1 State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Runlin Z
authors.initials: RZ
authors.lastname: Ma
mesh_terms: D000222:Adaptation, Physiological; D056809:Alveolar Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D002135:Calcium-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D018507:Gene Expression Regulation, Developmental; D020022:Genetic Predisposition to Disease; D006720:Homozygote; D008168:Lung / Q000196:embryology / Q000378:metabolism* / Q000503:physiopathology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009024:Morphogenesis; D009154:Mutation; D010641:Phenotype; D010743:Phospholipids / Q000378:metabolism; D001261:Pulmonary Atelectasis / Q000196:embryology / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D037662:Pulmonary Surfactant-Associated Protein A / Q000235:genetics / Q000378:metabolism; D037663:Pulmonary Surfactant-Associated Protein D / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D012127:Respiratory Distress Syndrome, Newborn / Q000196:embryology / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D012131:Respiratory Insufficiency / Q000196:embryology / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D015398:Signal Transduction; D014162:Transfection
chemical_list: D002135:Calcium-Binding Proteins; D010743:Phospholipids; D037662:Pulmonary Surfactant-Associated Protein A; D037663:Pulmonary Surfactant-Associated Protein D; C000609032:RCN3 protein, mouse
keywords: Cab45/Rcn/ERC45/calumenin (CREC) family; endoplasmic reticulum–associated degradation; neonatal respiratory distress; pulmonary surfactant; reticulocalbin 3